February 7, 2017

Hirschsprung’s disease (also called colonic aganglionosis) is a blockage of the large intestine due to improper muscle movement in the bowel. It is a congenital condition, which means it is present from birth. Hirschsprung’s disease affects one in every 5,000 babies.

Normally, the muscles in the bowel squeeze rhythmically to push faeces (poo) through to the rectum. In Hirschsprung’s disease, the nerves that control these muscles (ganglion cells) are missing from part of the bowel. This means that faeces cannot be pushed through the bowel in the usual way.

Sometimes the ganglion cells are missing throughout the whole large intestine and even parts of the small intestine. When the diseased section of the intestine reaches or includes the small intestine, it is called long-segment disease. When the diseased section includes only part of the large intestine, it is called short-segment disease.

The length of the affected part of bowel varies from child to child. Most commonly the rectum and/or sigmoid colon (the last parts of the large bowel) are affected. The entire colon is affected only very rarely.

The problems a child will experience with Hirschsprung’s disease depend on how much of the intestine has normal nerve cells present.

Causes

HD develops before a child is born. Normally, nerve cells grow in the baby’s intestine soon after the baby begins to develop in the womb. These nerve cells grow down from the top of the intestine all the way to the anus. With HD, the nerve cells stop growing before they reach the end.

It is unclear why the nerve cells stop growing; however, there is no evidence that it is caused by the mother’s actions or activities while she is pregnant.

Hirschsprung’s disease causes about 25% of all newborn intestinal blockages. It occurs five times more often in males than in females. Hirschsprung’s disease is sometimes linked to other inherited or congenital conditions, such as Down syndrome.

Risk Factors

Factors that may increase the risk of Hirschsprung’s disease include –

Having a sibling who has Hirschsprung’s disease – Hirschsprung’s disease can be inherited. If you have one child who has the condition, future biological children also might be at risk.

Being male – Hirschsprung’s disease is more common in males.

Having other inherited conditions – Hirschsprung’s disease is associated with certain inherited conditions, such as inherited heart problems and Down syndrome. It may also be associated with multiple endocrine neoplasia, type IIB — a syndrome that causes noncancerous tumors in the mucous membranes and adrenal glands (located above the kidneys) and cancer of the thyroid gland (located at the base of the neck). Roughly a third of children who have Hirschsprung’s disease have other abnormalities.

Symptoms

Symptoms of HD usually show up in very young children. Sometimes, however, they don’t appear until the teenage years or adult life. Symptoms that may be present in newborns and infants include –

  • Difficulty with bowel movements
  • Failure to pass meconium shortly after birth
  • Failure to pass a first stool within 24 – 48 hours after birth
  • Infrequent but explosive stools
  • Jaundice
  • Poor feeding
  • Poor weight gain
  • Vomiting
  • Watery diarrhea (in the newborn)

Symptoms in older children –

  • Constipation that gradually gets worse
  • Fecal impaction
  • Malnutrition
  • Slow growth
  • Swollen belly

Complications

  • Inflammation and infection of the intestines (enterocolitis) may occur before surgery, and sometimes during the first 1 – 2 years afterwards. Symptoms are severe, including swelling of the abdomen, foul-smelling watery diarrhea, lethargy, and poor feeding.
  • Perforation or rupture of the intestine
  • Short bowel syndrome, a condition that can lead to malnourishment and dehydration

Treatment

A procedure called serial rectal irrigation helps relieve pressure in (decompress) the bowel.

The abnormal section of colon must be taken out with surgery. Most commonly, the rectum and abnormal part of the colon are removed. The healthy part of the colon is then pulled down and attached to the anus.

Sometimes this can be done in one operation. However, it is often done in two parts. A colostomy is performed first. The other part of the procedure is done later in the child’s first year of life.

Pull through Surgery – For this operation, the end of the bowel that does not have nerve cells is completely or almost completely removed, and bowel that does contain nerve cells is attached to the anal opening. After surgery, stool comes from the normal anal opening. In some cases the pull through surgery can be done in a single operation, but if the child is very ill or the bowel is very dilated, it is more common to create a temporary ostomy.

Ostomy – This is a connection between the inside of the bowel and the skin on the abdomen. Colostomy means the connection is to the colon, whereas an ileostomy is a connection between the end of the small bowel and the skin. A small plastic bag is attached to the opening to collect stool.

Alternative Treatment

Sodium Supplements – Some patients, particularly those whose entire colon is affected by Hirschsprung disease, may need an ileostomy for many months and sometimes years The ileostomy can cause the body to lose sodium, something that the child needs in order to absorb nutrients from what they eat. For that reason, children with an ileostomy are often prescribed sodium supplements by their doctor. Doctors will also monitor the child’s growth carefully to make sure that they are getting the nutrients they need to develop normaly.

Vitamins – Prevents constipation.

Omega 3′s for brain health

 

Reference –

http://www.hopkinschildrens.org/hirschsprungs-disease.aspx

http://umm.edu/health/medical/ency/articles/hirschsprungs-disease

http://www.clickondetroit.com/health/family-hopes-to-educate-others-about-hirschsprungs-disease

http://my.clevelandclinic.org/childrens-hospital/health-info/diseases-conditions/hic-Hirschsprungs-Disease

http://www.healthline.com/health/hirschsprungs-disease

http://radiopaedia.org/articles/hirschsprung-disease

http://www.pediatricsurgerymd.org/AM/Template.cfm?Section=List_Of_Conditions1&template=/CM/ContentDisplay.cfm&ContentID=4284

http://www.stlouischildrens.org/diseases-conditions/hirschsprung-disease

http://www.aafp.org/afp/2006/1015/p1319.html

http://www.gosh.nhs.uk/medical-information-0/search-medical-conditions/hirschsprungs-disease

http://www.uptodate.com/contents/congenital-aganglionic-megacolon-hirschsprung-disease

http://www.seattlechildrens.org/medical-conditions/digestive-gastrointestinal-conditions/hirschsprung-disease-symptoms/

February 7, 2017

Henoch-Schönlein purpura is a rare disease in which the smallest blood vessels (the capillaries) swell and become tender. The inflammation itself then causes changes in the blood vessels. It is the most common form of childhood vascular inflammation (vasculitis).

Henoch-Schönlein Purpura causes blood vessels to become inflamed (irritated and swollen). This inflammation is called vasculitis. It usually affects the small blood vessels in the skin causing a rash that is called purpura. It can also affect blood vessels in the intestines and the kidneys.

The cause of HSP is unknown. It might be triggered by a bacterial or viral infection, medicines, insect bites, vaccinations or exposure to chemicals or cold weather. It occurs most often in the spring, usually after an upper respiratory tract infection such as a cold. HSP mostly affects children, but can affect adults. Sometimes it follows a throat or chest infection. It affects boys and girls equally. Half the children affected are under the age of five. Kidney involvement is more likely to be severe in older children and adults.

Sometimes HSP is occasionally also called Berger’s disease but this should not be confused with Buerger’s disease which is a different type of vasculitis

HSP usually affects children from two to 10 years of age, but it can happen in anyone. HSP itself is not contagious. Doctors don’t know how to prevent HSP yet.

Causes

Henoch-Schönlein purpura is caused by an abnormal immune system response in which the body’s immune system attacks the body’s own cells and organs. Usually, the immune system makes antibodies, or proteins, to protect the body from foreign substances such as bacteria or viruses. In HSP, these antibodies attack the blood vessels. The factors that cause this immune system response are not known. However, in 30 to 50 percent of cases, people have an upper respiratory tract infection, such as a cold, before getting HSP.2 HSP has also been associated with

  • Infectious agents such as chickenpox, measles, hepatitis, and HIV viruses
  • Medications
  • Foods
  • Insect bites
  • Exposure to cold weather
  • Trauma

Genetics may increase the risk of HSP, as it has occurred in different members of the same family, including in twins.

Risk Factors

Factors that may increase the risk of developing Henoch-Schonlein purpura include –

  • Age – The disease affects primarily children and young adults with the majority of cases occurring in children between 2 and 6 years of age.
  • Sex – Henoch-Schonlein purpura is slightly more common in boys than girls.
  • Race – White and Asian children are more likely to develop Henoch-Schonlein purpura than black children are.
  • Time of year – Henoch-Schonlein purpura strikes mainly in autumn, winter and spring but rarely in summer.

Symptoms

The symptoms usually begin suddenly and may include –

  • Bloody stools
  • Fever
  • Headache
  • Joint pain
  • Loss of appetite
  • Painful menstruation
  • Red or purple spots on the skin. These usually appear on the buttocks, lower legs and elbows
  • Stomach cramps, nausea, vomiting or diarrhea

The disease can affect the joints, kidneys, digestive system and – in rare cases – the brain and spinal cord. There are different forms of the disease, which affect different parts of the body. For example –

  • Schönlein’s purpura affects the skin and joints but not the digestive system
  • Henoch’s purpura causes spots on the skin and severe abdominal problems. Persons with this form of the disease do not have joint symptoms.

Complications

Complications associated with Henoch-Schonlein purpura include –

Kidney damage – The most serious complication of Henoch-Schonlein purpura is kidney damage. Occasionally the damage is severe enough that dialysis or a kidney transplant may be needed.

Bowel obstruction – In rare cases, Henoch-Schonlein purpura can cause intussusception — a condition in which a section of the bowel folds into itself like a telescope, which prevents matter from moving through the bowel.

Treatment

Symptoms of HSP usually last for about a month. Most of the time, it goes away on its own without treatment. To help your child feel better, the doctor may recommend certain medications, such as –

  • Antibiotics to treat the causative infection, if applicable
  • Painkillers (such as acetaminophen)
  • Anti-inflammatory medicines (such as ibuprofen) to relieve joint pain and inflammation
  • Corticosteroids (such as prednisone) for severe abdominal pain or kidney disease

HSP usually gets better on its own without causing lasting problems. About half of people who have had HSP once will get it again. A few people will have kidney damage because of HSP. This may occur in the first week or so of illness, but there may be a delay of weeks or months before it appears. Your child’s doctor will want to test urine samples and blood pressure several times after the HSP goes away to check for kidney problems. These checks should go on for at least six months and some doctors recommend a blood pressure and urine check every year for life.

Alternative Treatment

Foot Bath – This therapy combines traditional Chinese herbs with the warm foot bath. The herbs we choose are based on the patient’s specific condition. The effective ingredients can stimulate the meridians on feet, thus the whole blood vessels can be unlocked. More over, they have the function of fighting against inflammation in blood vessels, thus treating HSP from the root.

Immunotherapy – There are six steps of this therapy. They inhibit the inflammations and restore normal immune system. It is also involve in TCM. Since most TCM come from nature, and these remedies are external application, they are very safe for children.

Hot Compress Therapy – This is an external application of Chinese herb medicine. According to patient’s specific disease condition, kidney doctors would choose the herbs and blend them together sufficiently. During the treatment process, we compress the powder of the herbs on kidney area, transmitting the medicine ingredients to the renal lesion by electromagnetic wave.

 

Reference –

http://familydoctor.org/familydoctor/en/diseases-conditions/henoch-schonlein-purpura.html

http://umm.edu/health/medical/ency/articles/henochschonlein-purpura

http://pedsinreview.aappublications.org/content/35/10/447

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/henoch-schonlein-purpura

https://www.cedars-sinai.edu/Patients/Health-Conditions/Henoch-Schonlein-Purpura.aspx

http://bestpractice.bmj.com/best-practice/monograph/110.html

http://www.gosh.nhs.uk/medical-information-0/search-medical-conditions/henoch-sch-nlein-purpura-hsp

http://www.dermnetnz.org/vascular/hsp.html

http://www.vasculitis.org.uk/about-vasculitis/henoch-schonlein-purpura

http://patient.info/doctor/henoch-schonlein-purpura-pro

http://my.clevelandclinic.org/services/orthopaedics-rheumatology/diseases-conditions/hic-henoch-schonlein-purpura

http://www.vasculitisfoundation.org/education/forms/henoch-schonlein-purpura/

February 7, 2017

Hemolytic Uremic Syndrome (HUS), commonly referred to as “Hamburger Disease”, is a disease that affects the kidneys and other organs. It poses a substantial threat to Canadian children as one of the leading causes of both acute and chronic kidney failure.

HUS is considered a syndrome because it is a combination of findings that may have different causes. In most cases, HUS occurs after a severe bowel infection with certain toxic strains of the bacteria called E. coli. It may also occur in response to certain medicines, but this is rare. Even more rarely, HUS occurs for unknown reasons. This fact sheet primarily focuses on the type of HUS that occurs in infants and children as a result of an E. coli infection.

It is a condition that affects the blood and blood vessels. It results in the destruction of blood platelets (cells involved in clotting), a low red blood cell count (anemia) and kidney failure due to damage to the very small blood vessels of the kidneys. Other organs, such as the brain or heart, may also be affected by damage to very small blood vessels.

HUS is a kidney condition that happens when red blood cells are destroyed and block the kidneys’ filtering system. Red blood cells contain hemoglobin—an iron-rich protein that gives blood its red color and carries oxygen from the lungs to all parts of the body. When the kidneys and glomeruli—the tiny units within the kidneys where blood is filtered—become clogged with the damaged red blood cells, they are unable to do their jobs. If the kidneys stop functioning, a child can develop acute kidney injury—the sudden and temporary loss of kidney function. Hemolytic uremic syndrome is the most common cause of acute kidney injury in children.

Though hemolytic uremic syndrome is a serious condition, getting timely and appropriate treatment leads to a full recovery for most people, especially young children.

Causes

HUS develops when Escherichia coli (E. coli) bacteria lodged in the digestive tract make toxins that enter the bloodstream and start to destroy red blood cells. Most cases of HUS occur after an infection of the digestive tract by the E. coli bacterium, which is found in foods like meat, dairy products, and juice when they are contaminated. Some people have contracted HUS after swimming in pools or lakes contaminated with feces.

Infection of the digestive tract is called gastroenteritis and may cause a child to vomit and have stomach cramps and bloody diarrhea. Most children who have gastroenteritis recover fully in 2 or 3 days and do not develop HUS.

E.coli O157:H7 can be found in –

  • Undercooked meat, most often ground beef
  • Unpasteurized, or raw, milk
  • Unwashed, contaminated raw fruits and vegetables
  • Contaminated juice
  • Contaminated swimming pools or lakes

Less common causes, sometimes called atypical hemolytic uremic syndrome, can include –

  • Taking certain medications, such as chemotherapy
  • Having other viral or bacterial infections
  • Inheriting a certain type of hemolytic uremicsyndrome that runs in families

More information about foodborne illnesses and the digestive system is provided in the NIDDK health topic, foodborne illnesses.

Risk Factors

Those most at risk of developing hemolytic uremic syndrome are –

  • Children under 5 years of age
  • People who have certain genetic changes that make them more susceptible

Young children and elderly adults are the most likely to be seriously ill from hemolytic uremic syndrome.

Symptoms

HUS often begins with vomiting and diarrhea, which may be bloody. Within a week, the person may become weak and irritable. Persons with this condition may urinate less than normal. Urine output may almost stop.

Red blood cell destruction leads to symptoms of anemia.

Early symptoms –

  • Blood in the stools
  • Irritability
  • Fever
  • Lethargy
  • Vomiting
  • diarrhea
  • Weakness

Later symptoms –

  • Bruising
  • Decreased consciousness
  • Low urine output
  • No urine output
  • Pallor
  • Seizures — rare
  • Skin rash that looks like fine red spots (petechiae)
  • Yellow skin (jaundice)

Complications

  • Blood clotting problems
  • Hemolytic anemia
  • Kidney failure
  • Nervous system problems
  • Too few platelets (thrombocytopenia)
  • Uremia

Treatment

  • Fluid replacement – Lost fluid and electrolytes need to be carefully replaced because the kidneys aren’t removing fluids and waste as efficiently as normal.
  • Red blood cell transfusions – If patients don’t have enough red blood cells, they may feel chilled, fatigued and short of breath. They may have a rapid heart rate, yellow skin and dark urine. Red blood cell transfusions, given through an intravenous (IV) needle, may help reverse these signs and symptoms.
  • Platelet transfusions – If the patient is bleeding or bruising easily, platelet transfusions can help your blood clot more normally. Like red blood cell transfusions, platelet transfusions are given through an IV needle.
  • Plasma exchange – Plasma is the part of blood that supports the circulation of blood cells and platelets. Sometimes a machine is used to clear the blood of its own plasma and replace it with fresh or frozen donor plasma. This process is called plasmapheresis.
  • Kidney dialysis – Sometimes dialysis is needed to filter waste and excess fluid from the blood. Dialysis is usually a temporary treatment until the kidneys begin functioning adequately again. If the kidney damage is significant, however, permanent kidney failure — requiring long-term dialysis or a kidney transplant — is possible.

Alternative Treatment

 

Reference –

https://www.nlm.nih.gov/medlineplus/ency/article/000510.htm

http://www.merckmanuals.com/professional/hematology-and-oncology/thrombocytopenia-and-platelet-dysfunction/thrombotic-thrombocytopenic-purpura-(ttp)-and-hemolytic-uremic-syndrome-(hus)

http://www.niddk.nih.gov/health-information/health-topics/kidney-disease/hemolytic-uremic-syndrome-in-children-hus/Pages/facts.aspx

http://patient.info/doctor/Haemolytic-Uraemic-Syndrome.htm

http://www.merckmanuals.com/professional/hematology-and-oncology/thrombocytopenia-and-platelet-dysfunction/thrombotic-thrombocytopenic-purpura-(ttp)-and-hemolytic-uremic-syndrome-(hus)

http://medicalxpress.com/news/2015-11-hemolytic-uremic-syndrome-treatment-regimen.html

http://medind.nic.in/ibv/t09/i12/ibvt09i12p1075.pdf

http://www.nejm.org/doi/full/10.1056/NEJMra0902814

http://www.aafp.org/afp/2006/0915/p991.html

http://library.med.utah.edu/ed/ahus.html

http://www.uptodate.com/contents/overview-of-hemolytic-uremic-syndrome-in-children

https://www.rareconnect.org/en/community/atypical-hemolytic-uremic-syn

February 7, 2017

Hemochromatosis (HH) is a disease that results from excessive amounts of iron in the body (iron overload).

Hereditary (genetic) hemochromatosis (HHC) an inherited disorder of abnormal iron metabolism. Individuals with hereditary hemochromatosis absorb too much dietary iron. Once absorbed, the body does not have an efficient way of excreting iron excesses. Over time, these excesses build to a condition of iron overload, which is a toxic to cells. Glands and organs, including the liver, heart, pituitary, thyroid, pancreas, synovium (joints) and bone marrow burdened with excess iron cannot function properly. Symptoms develop and disease progresses.

As many as 1 in 200 Americans are believed to carry both copies of the gene for hemochromatosis, and it is estimated that about half of them will eventually develop complications. That puts it roughly on a par with type 1 diabetes for prevalence. Like type 2 diabetes, it is severely underdiagnosed.

Types of Hemochromatosis

Hemochromatosis is classified by type depending on the age of onset and other factors such as genetic cause and mode of inheritance.

Hemochromatosis type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) are adult-onset disorders. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause

Type 2 hemochromatosis is a juvenile-onset disorder. Iron accumulation begins early in life, and symptoms may begin to appear in childhood. By age 20, decreased or absent secretion of sex hormones is evident. Females usually begin menstruation in a normal manner, but menses stop after a few years. Males may experience delayed puberty or sex hormone deficiency symptoms such as impotence. If the disorder is untreated, heart disease is evident by age 30.

Onset of type 3 hemochromatosis is usually intermediate between types 1 and 2. Symptoms generally begin before age 30.generally begin before age 30.

In rare cases, iron overload begins before birth. These cases are called neonatal hemochromatosis. This type of hemochromatosis progresses rapidly and is characterized by liver damage that is apparent at birth or in the first day of life. The neonatal form causes rapid iron buildup in a baby’s liver that can lead to death.

Causes

Hemochromatosis is a hereditary disorder, which means it is passed down from parents to children through their genes. Hemochromatosis is mainly caused by a defect in the HFE gene. It is also known as primary hemochromatosis.

Some people get a copy of the HFE gene defect from just one parent. They are called “carriers” because they carry the defective gene and can pass it on to their children. Carriers usually do not get sick. People who get the HFE gene defect from both parents have a greater chance of getting the disease.

There are other types of hemochromatosis that are not caused by the HFE gene defect — including secondary, juvenile, and neonatal hemochromatosis – but they are less common than the primary form. Secondary hemochromatosis can be caused by disorders such as thalassemia, anemia, chronic alcoholism, and other conditions. Juvenile and neonatal hemochromatosis are caused by other types of gene defects.

Risk Factors

The known risk factors for hemochromatosis are:

Possessing two copies of a mutated HFE gene – the greatest risk factor for hereditary hemochromatosis. The person inherits one copy of the mutated HFE gene from each parent.

Family history – anybody who has a close relative (parent, offspring, brother or sister) with hemochromatosis is significantly more likely to develop it compared to other people.

Ancestry – people of British, Scandinavian Dutch, German, Irish and French ancestry have a higher risk of developing hemochromatosis compared to others. Their risk of having the HFE gene mutation is greater.

Gender – men are significantly more likely to develop hemochromatosis compared to women. Signs and symptoms tend to appear earlier on in life in males than females. This is because women lose iron during menstruation and pregnancy. A woman’s risk increases after the menopause or a hysterectomy. The male-to-female ratio is 1.8:1 (out of every 28 people with hemochromatosis, 18 are male and 10 are female).

Symptoms

A symptom is something the patient feels or reports, while a sign is something other people, including a doctor, may detect. For example, a headache may be a symptom while a rash may be a sign.

As signs and symptoms may be mild and could also be indications of other illnesses and conditions, identifying hemochromatosis is often not straightforward.

  • The main symptoms include:
  • Abdominal pain
  • Females may stop menstruating
  • High blood sugar levels
  • Hypothyroidism (low thyroid function)
  • Loss of libido (sex drive) and male impotence
  • Pain in the joints
  • Reduction in size of testicles
  • Skin becomes bronzed (has a tanned look)
  • Tiredness (fatigue)
  • Weakness
  • Weight loss

Complications

As the disorder progresses, the following conditions may develop:

  • Enlarged liver
  • Cirrhosis (scarring of the liver)
  • Liver cancer
  • Liver failure
  • Arthritis
  • Osteoporosis
  • Diabetes (from damage to the pancreas)
  • Irregular heartbeat
  • Enlarged heart
  • Congestive heart failure
  • Impotence
  • Early menopause
  • Hypothyroidism
  • Damage to adrenal glands
  • Enlarged spleen

Treatment

  • Venesection (phlebotomy) – iron-rich blood is removed from the body regularly, just as if the patient were donating blood. In this case the aim is to bring iron levels down to normal. How much blood is taken and how often depends on the patient’s age, overall health and the severity of the iron overload. In most cases blood is removed weekly until levels are back to normal. When iron levels build up again the patient will need venesection treatment again.

Although venesection cannot reverse the symptoms of cirrhosis, it can improve symptoms such as nausea, abdominal pain and fatigue.

  • Medication – the patient may be given a drug that binds iron, which is then excreted from the body.

If hemochromatosis is diagnosed and treated early, before too much excessive iron accumulates, the patient should have a normal lifespan, experts say.

Alternative Treatment

Excess iron and treatment – Getting iron levels down is very important to the outcome of hemochromatosis. A therapeutic phlebotomy or blood transfusion are usually accomplished this. Blood donations are done every eight weeks; sever conditions may require up to eight donations per month. Some medications may help also. The goal is to get iron levels down.

Herbal Therapy – Here are some herbal therapies that have been known to be useful in treating iron overload.

  • Dandelion—reduces constipation caused by excess iron conditions.
  • Wild Hyssop—regulates blood sugar, reduces pain and inflammation surrounding nerve tissues needing iron supply to vital organs needing nutrients.
  • Milk Thistle—reduces the iron storage in the body and lowers blood sugar levels.

Chelation Therapy – Chelating therapy removes excess minerals, and toxic materials from the body through the use of drugs; making it easier for them to tolerate phlebotomy.

EDTA Chelation Therapy – EDTA is used to remove heavy metals from the body, with IV therapy; given under supervision of medical supervision.

Calcium – Taking 300 mg of calcium per day with a meal is a simple way to block the absorbed iron, and reduce it about 40%. Some people do build up a tolerance to calcium, so regular blood tests are needed.

Vitamins and minerals

  • Vitamin B6—blocks absorption of iron, especially when taking vitamin C.
  • Avoid Vitamin C—limit taking vitamin c supplements over 500mg, eat more fresh vegetables and fruit containing vitamin C instead.
  • Vitamin E—antioxidant used as a blood thinner (400-800IU)
  • Manganese—protects against damage from excess iron.

Black Tea – Drinking black tea may reduce iron absorption, and reduces amount of frequent phlebotomies patients may have. Green tea is also powerful as a chelator to remove iron.

 

Reference –

http://www.lifeextension.com/protocols/metabolic-health/hemochromatosis/Page-01

https://my.clevelandclinic.org/health/diseases_conditions/hic_hemochromatosis

http://familydoctor.org/familydoctor/en/diseases-conditions/hereditary-hemochromatosis.html

https://www.aasld.org/sites/default/files/guideline_documents/Hemochromatosis2011.pdf

https://www.genome.gov/10001214

http://www.hopkinschildrens.org/hemochromatosis.aspx

http://www.aafp.org/afp/2013/0201/p183.html

http://www.yourgenesyourhealth.org/hc/whatisit.htm

http://www.hemochromatosisdna.com/about-the-disease/signs-and-symptoms

http://www.liver.ca/liver-disease/types/hemochromatosis.aspx

http://www.healthline.com/health/hemochromatosis

http://www.diabetes.org/living-with-diabetes/complications/related-conditions/hemochromatosis.html?referrer=https://www.google.co.in/

February 7, 2017

Granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis, is a multisystem systemic necrotising non-caseating granulomatous vasculitis affecting small to medium sized arteries, capillaries and veins, with a predilection for the respiratory system and kidneys.

What is Vasculaties? Vasculitis is a general term that refers to inflammation of the blood vessels. When inflamed, the blood vessel may become weakened and stretch forming an aneurysm, or become so thin that it ruptures resulting in bleeding into the tissue. Vasculitis can also cause blood vessel narrowing to the point of closing off the vessel entirely. This can cause organs to become damaged from loss of oxygen and nutrients that were being supplied by the blood.

Granulomatosis with polyangiitis (Wegener’s) is believed to be an autoimmune disorder. This means the body’s immune defenses mistakenly attack the body’s own cells and tissues. In this case, the misdirected immune attack is aimed at the blood vessels. This triggers inflammation and damage.

In this disorder, small-sized blood vessels in the nose, sinuses, ears, lungs and kidneys become inflamed and damaged. Other areas may also be affected in some cases. It can also produce a type of inflammatory tissue known as a granuloma that’s found around the blood vessels. Granulomas can destroy normal tissue.

Three areas in the body are affected most commonly –

  • Upper airways (including the sinuses, trachea and nose) – In the upper airways, tissue destruction causes chronic (long-lasting) nasal and sinus problems. Many people with Granulomatosis with polyangiitis (Wegener’s) first see their doctors because of sinusitis, persistent runny nose or frequent bloody nose.
  • Lungs – In most people with Granulomatosis with polyangiitis (Wegener’s), inflammation targets the lungs as well. This causes a respiratory illness. Symptoms include coughing, shortness of breath, wheezing or coughing up blood.
  • Kidneys – Kidney damage affects most people with Granulomatosis with polyangiitis (Wegener’s). But in many cases, this damage is mild and does not cause any symptoms. In some people, however, the kidney damage is more severe. It may cause kidney failure.

Wegener’s granulomatosis is most common in middle-aged adults, with an average age of onset between 40 and 65 years. It is rare in children, but has been seen in infants as young as 3 months old. Whites are more likely than blacks to develop Wegener’s granulomatosis.

Causes

Experts do not know what causes Wegener’s granulomatosis. Most agree that it develops as a result of an initial inflammation-causing event that provokes an abnormal immune system reaction, leading to inflamed and constricted blood vessels and granulomas (inflammatory tissue masses).

Many scientists tend to believe that an initial infection may be the start of the whole event. Studies have shown that about 50% of patients with Wegener’s granulomatosis had an infection. Some people believe that there may be other contributory factors, such as:

  • Environmental toxins
  • A genetic predisposition
  • A combination of both

Risk Factors

According to one estimate, the frequency of Wegener’s granulomatosis is one in 30,000 to 50,000 individuals in the United States. However, because cases of Wegener’s granulomatosis often go unrecognized, the disorder is under-diagnosed making it difficult to determine its true frequency in the general population. Wegener’s granulomatosis predominately affects Caucasians.

Granulomatosis with polyangiitis can occur at any age. It most often affects people between the ages of 40 and 65.

Symptoms

Sinus and lung symptoms are most common in GPA. Other early symptoms include fever, night sweats, fatigue and a general ill feeling (malaise). For some people, the disease is limited to the respiratory system and doesn’t involve the kidneys. Kidney involvement usually doesn’t cause symptoms early in the course of the disease. It may be detected only by blood and urine tests. Over time, kidney failure and anemia often occur.

Wegener’s granulomatosis signs and symptoms can develop either gradually or suddenly. Initial symptoms can vary widely, and diagnosis may sometimes be delayed because of their non-specific nature. The first symptom in most patients is rhinitis – runny and stuffy nose.

Signs and symptoms may include –

  • Sinus pain and inflammation
  • Runny nose, with pus-filled discharge
  • Nosebleeds
  • Fever
  • General ill feeling (malaise)
  • Unintended weight loss
  • Ear infections
  • Cough
  • Chest pain
  • Coughing up blood
  • Shortness of breath
  • Joint aches and swelling
  • Blood in urine
  • Skin sores
  • Eye redness, burning or pain

Other common symptoms include –

  • Lungs – breathlessness, wheeze, dry cough or coughing up blood
  • Skin – rashes, ulcers, and necrosis (death of tissue)
  • Eyes – red (blood shot) eyes, painful, dry or gritty eyes, visual loss or other changes in vision
  • Nerves – loss of sensation, weakness, unusual painful symptoms in the hands and feet (hotness, pins and needles or “electric shocks”) and rarely paralysis or stroke
  • Bowels – Diarrhoea, bleeding and abdominal pain.

Complications

Complications most often occur when the disease is not treated. People with GPA develop tissue damage in the lungs, airways, and the kidneys. Kidney involvement may result in blood in the urine and kidney failure. Kidney disease can quickly get worse. Kidney function may not improve even when the condition is controlled by medicines. If untreated, kidney failure and possibly death occur in most cases.

Other complications may include –

  • Eye swelling
  • Lung failure
  • Coughing up blood
  • Nasal septum perforation (hole inside the nose)
  • Side effects from medicines used to treat the disease

Treatment

Medications

  • Corticosteroids – such as prednisone may be prescribed for initial signs and symptoms. In a few cases this is the only medication needed.
  • Other immunosuppressive drugs – such as cyclophosphamide (Cytoxan), azathioprine (Imuran) or methotrexate (Rheumatrex) is prescribed as well in most cases. The aim is to stop the body’s immune system from overreacting.
  • Rituximab (Rituxan) – this medication, which was originally designed to treat non-Hodgkin’s lymphoma (a type of cancer), was later approved for rheumatoid arthritis treatment. Rituximab reduces the number of B cells in the body – B cells are involved with inflammation. If standard treatments are not effective some doctors may prescribe Rituximab.

Surgery – if the Wegener’s granulomatosis patient has suffered kidney failure the doctor may recommend a kidney transplant.

Alternative Treatment

 

Reference –

http://www.uveitis.org/docs/dm/wegeners_granulomatosis_diagnosis_management.pdf

http://www.encyclopedia.com/topic/Wegeners_Granulomatosis.aspx

http://www.medicalnewstoday.com/articles/187807.php

http://www.mayoclinic.org/diseases-conditions/granulomatosis-with-polyangiitis/home/ovc-20167226

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/wegeners-granulomatosis

http://www.msdmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/vasculitis/granulomatosis-with-polyangiitis-(gpa)

https://umm.edu/health/medical/ency/articles/wegeners-granulomatosis

http://www.myvmc.com/diseases/wegeners-granulomatosis/

http://www.sciencedirect.com/science/article/pii/S0030665713000383

https://www.nlm.nih.gov/medlineplus/ency/article/000135.htm

http://www.ajronline.org/doi/full/10.2214/AJR.08.1837

http://emedicine.medscape.com/article/332622-overview

http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Granulomatosis-with-Polyangitis-Wegners

http://www.hopkinsvasculitis.org/types-vasculitis/wegeners-granulomatosis/

http://www.nhs.uk/Conditions/wegeners-granulomatosis/Pages/Introduction.aspx

https://my.clevelandclinic.org/health/diseases_conditions/hic_Wegeners_Granulomatosis

February 7, 2017
February 7, 2017

Gaucher disease is a rare inherited metabolic disorder characterized by anemia, mental and neurologic impairment, yellowish pigmentation of the skin, enlargement of the spleen, and bone deterioration resulting in pathological fractures.

Gaucher disease was initially described in 1882 by French physician Philippe Charles Ernest Gaucher. Normally, the body makes an enzyme called glucocerebrosidase that breaks down and recycles glucocerebroside – a normal part of the cell membrane. People who have Gaucher disease do not make enough glucocerbrosidase. This causes the specific lipid to build up in the liver, spleen, bone marrow and nervous system interfering with normal functioning.

Gaucher disease occurs in about 1 in 50,000 to 1 in 100,000 individuals in the general population. Type 1 is found more frequently among individuals who are of Ashkenazi Jewish ancestry. Type 1 Gaucher disease is present 1 in 500 to 1 in 1000 people of Ashkenazi Jewish ancestry, and approximately 1 in 14 Ashkenazi Jews is a carrier. Type 2 and Type 3 Gaucher disease are not as common.

Types of Gaucher’s Disease

There are five main types of Gaucher disease, each with different manifestations. These types are described below.

Type 1 – Type 1 is the most common form of the disease. It can affect people at any age and its symptoms vary widely from mild to severe.

Type 2 – Type 2 is known as the infantile or acute neuropathic form of Gaucher disease. Symptoms usually appear before age 2 and progress rapidly. Children with type 2 Gaucher disease have some of the symptoms of type 1. These may include enlarged liver and spleen, lowered number of red blood cells (anemia) leading to weakness and tiredness, lowered number of platelets leading to bleeding and bruising, and lung disease.

Type 3 – Type 3 Gaucher disease is known as the juvenile or chronic neuropathic form. Symptoms often begin before age 2, though this is variable. Usually the symptoms associated with type 3 progress more slowly than with type 2. While some people with type 3 Gaucher disease die in childhood, others can live into their 30s or 40s.

Perinatal-Lethal Form – The perinatal-lethal form is a rare but severe form of Gaucher disease. This form usually leads to death in utero or shortly after birth.

Cardiovascular Form – As the name implies, the cardiovascular form of Gaucher disease causes symptoms involving the heart, notably a hardening of the mitral and aortic valves. If this symptom is severe, heart valve replacement may be required.

Causes

Gaucher’s disease is caused by a recessive mutation of the gene called GBA, located on chromosome 1. The GBA gene tells the body to produce glucocerebrosidase. Glucocerebrosidase, an enzyme (protein), breaks down a type of fat (lipid) known as glucosylceramide into sugar and simple fats, which the body uses for energy.

If the GBA gene is faulty there is a deficiency of the enzyme glucocerebrosidase, which leads to an excessive accumulation of glucosylceramide, which starts to collect inside the cells of the brain, bone marrow, lungs, spleen and liver, and interferes with their normal functioning.

Inheritence – A baby inherits Gaucher’s disease in an “autosomal recessive manner”. If a baby inherits a faulty gene from each parent, i.e. has two faulty genes, he/she has Gaucher’s disease. Both parents need to be carriers for their offspring to develop Gaucher’s disease.

If both parents are carriers, each pregnancy has a:

  • 25% chance of producing an offspring with Gaucher’s disease
  • 50% risk of having a child who is a carrier
  • 25% chance the child is neither affected nor a carrier (if he/she inherits a properly-functioning gene from each parent).

Symptoms

A symptom is something the patient feels and describes, such as a headache, while a sign is something others can detect, e.g. a rash.

Most patients describe their first symptom as a swollen stomach. This is usually one of the first warning signs that sends patients to the doctor – an enlarged abdomen. This is because the spleen has swollen.

One of the spleen’s functions is to weed out old blood cells. When the spleen enlarges too much, sometimes to 25 times its normal size, it weeds out too many blood cells, including good ones. This can lead to anemia. Patients with insufficient blood cells suffer from fatigue, because they are not getting enough oxygen and energy. If the spleen has taken out too many platelets, which are essential for coagulation (clotting), the patient will bleed and bruise more.

People with Gaucher’s disease do not all have the same symptoms.

Gaucher’s disease Type 1 – Signs and symptoms may include –

  • Anemia
  • Delayed puberty
  • Fatigue
  • Frequent nosebleeds
  • Hepatomegaly – enlarged liver
  • Osteopenia (bone thinning), bone fractures, and bone pain. Damage to the shoulder or hip joints are common.
  • Osteoporosis – demineralization of the bones
  • Pingueculae – yellow spots in the eyes
  • Splenomegaly – enlarged spleen
  • Thrombocytopenia – low blood platelet numbers, resulting in easy bruising and slow clotting times (easy bleeding)

Type 1 Gaucher’s disease is most prevalent in the Ashkenazi Jewish population.

Gaucher’s disease Type 2 – Signs and symptoms may include:

  • All those possible in Type 1, plus..
  • Mental retardation
  • Apnea – breathing stops temporarily during sleep
  • Dementia
  • Seizures
  • Rigidity

Gaucher’s disease Type 3 – Signs and symptoms may include:

  • All those possible in Type 1, plus..
  • Mental retardation
  • Dementia
  • Convulsions
  • Ocular muscle apraxia – abnormal eye movements
  • Myoclonus – muscle twitches

Perinatal-Lethal Form – Infants with the disease have symptoms including enlarged liver and spleen, lowered number red blood cells and platelets, neurological problems, skin abnormalities, and often distinct facial features.

 

Complications

Gaucher’s disease may increase the risk of –

  • Growth delays in children
  • Gynecological and obstetric problems
  • Parkinson’s disease
  • Cancers such as myeloma, leukemia and lymphoma
  • Organ damage
  • Osteopenia
  • Ruptured spleen
  • Severe swelling (edema)
  • Increased bleeding

Treatment

Enzyme replacement therapy (ERT) – The deficient glucocerebrosidase is replaced with intravenous recombinant glucocerebrosidase (imiglucerase). ERT is more effective for most patients with Type 1, and some with Type 3. ERT can help prevent hepatomegaly (enlarged liver) and splenomegaly (enlarged spleen), improve bone density as well as blood platelet count. ERT does not treat problems with the nervous system (brain damage) in patients with Types 2 and 3.

Substrate reduction therapy (SRT) – The aim here is to reduce the production and buildup of substrate (waste material) within cells. SRT reduces the amount of waste a cell makes so that for patients who are deficient in glucocerebrosidase, the glucocerebrosidase they do have is better able to prevent the waste from building up within cells.

Bone marrow transplant – Also known as stem cell transplant, replaces bone marrow that has been damaged by Gaucher’s with healthy bone marrow stem cells. Bone marrow is a spongy tissue that exists in the hollow centers of some bones. Bone marrow cells produce blood cells, including red and white blood cells, and platelets (which help stop bleeding).

Inhibit production of the problem substances – Oral medications, such as miglustat (Zavesca) and eliglustat (Cerdelga), appear to interfere with the production of the fatty substances that build up in people with Gaucher’s disease. Nausea and diarrhea are common side effects.

Spleen removal – Before enzyme replacement therapy became available, removing the spleen was a common treatment for Gaucher’s disease. Currently, this procedure is typically reserved as a last resort.

Psychological Care – It’s also important to consider the mental and emotional impact that Gaucher disease can place on patients and their families. Professional counseling can help patients better manage the difficulties of their disease and the lifestyle changes that may be required.

 

Reference –

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=355

https://www.gaucher.org.uk/

http://www.medicalnewstoday.com/articles/263370.php

http://rarediseases.org/rare-diseases/gaucher-disease/

https://www.genome.gov/25521505

https://www.gauchercare.com/en/patient/about/TypesOfGaucher.aspx

http://ghr.nlm.nih.gov/condition/gaucher-disease

http://emedicine.medscape.com/article/944157-overview

http://www.gaucherdisease.org/

February 7, 2017

In the beginning of the twentieth century, developmental biology and genetics were two separate disciplines. The word epigenetics was coined by Waddington to link the two fields. Epigenetics literally means “on top of or in addition to genetics.” It is defined as the study of mechanisms or pathways that initiate and maintain heritable patterns of gene expression and gene function without changing the DNA sequence.

Many human diseases are caused in whole or in part by environmental factors. It has been accepted that environmental chemicals can cause many of these diseases through changes in the genome (i.e., genetic effects). However, environmental chemicals can also cause effects in a variety of other ways. The study of these enduring changes, where life meets the genome, is epigenetics. Epigenetic discoveries have a great impact upon the understanding of child development, mental health, and how public health and well-being can be maintained in a changing world.

What id Epigenetic?

The term epigenetics refers to heritable changes in gene expression (active versus inactive genes) that does not involve changes to the underlying DNA sequence; a change in phenotype without a change in genotype. Epigenetic change is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. Epigenetic modifications can manifest as commonly as the manner in which cells terminally differentiate to end up as skin cells, liver cells, brain cells, etc. Or, epigenetic change can have more damaging effects that can result in diseases like cancer.

In other words, Epigenetics refers to the addition or deletion of a methyl group to a DNA base, turning the gene on or off, or to packaging of the chromatin structure by silencing or opening regions of the genome by winding or unwinding the DNA around histones.

Epigenetic and developmental epigenetic changes happen in all humans as part of normal growth, development, and aging. Some of the changes can alter the risk of developing certain diseases.

At least three systems including DNA methylation, histone modification and non-coding RNA (ncRNA)-associated gene silencing are currently considered to initiate and sustain epigenetic change. Numerous researches are continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases.

  • DNA Methylation – DNA methylation is a chemical process that adds methyl group to DNA. This prevents certain genes from being expressed. Methylation can be transient and can change rapidly during the life span of a cell or organism, or it can be essentially permanent once set early in the development of the embryo.
  • Histone Modification – Histones are proteins that are the primary components of chromatin, which is the complex of DNA and proteins that makes up chromosomes. Histones act as a spool around which DNA can wind. When histones are modified after they are translated into protein (i.e., post-translation modification), they can influence how chromatin is arranged, which, in turn, can determine whether the associated chromosomal DNA will be transcribed. There are two main ways histones can be modified: acetylation and methylation. Acetylation is usually associated with active chromatin, while deacetylation is generally associated with heterochromatin. On the other hand, histone methylation can be a marker for both active and inactive regions of chromatin.
  • RNA-Associated Silencing – Genes can also be turned off by RNA when it is in the form of antisense transcripts, non-coding RNAs, or RNA interference. RNA might affect gene expression by causing heterochromatin to form, or by triggering histone modifications and DNA methylation.

Causes of Epigenetic Changes

Interactions with the environment can cause epigenetic changes that affect how the genes work. These interactions include behaviors like smoking, eating, drinking, exercise, and exposure to natural and manufactured chemicals in air, water, and food.

Environmental Factors – Environmental factors are one cause. These can include, but are not limited to –

  • Exercise
  • Diet
    • High-fat diet – Studies show that pregnant mothers’ high-fat diets to epigenetic changes and later development of tumors in their offspring.
    • Lack of essential vitamins and nutrients, such as choline, B vitamins, and folic acid. An NICHD-supported animal study linked lack of B vitamins and folate in pregnant mothers’ diets with epigenetic changes, obesity, and heart disease in their offspring.
    • Intake of resveratrol – This substance, found in red grapes and red wine, may help protect against cancer.
  • Nicotine, the drug that makes cigarettes addictive
  • Alcohol
  • Chemicals in the living space or workplace – Asbestos, a toxic chemical that is sometimes found in older buildings. Bisphenol A (BPA), a chemical in many plastic containers, such as water bottles.
    • Heavy metals (e.g., cadmium) can disrupt DNA methylation.
    • Vinclozolin, a widely used pesticide, can alter DNA methylation in exposed laboratory animals. These changes persist in unexposed offspring through several generations.
    • Deficiencies in folate and methionine, both of which are involved in cellular processes that supply methyl groups needed for DNA methylation, can change the expression (imprinting) of growth factor genes
  • Medications

These environmental factors are only a few examples of things that can cause epigenetic changes. Many other environmental factors, known and unknown, can cause epigenetic changes.

Some epigenetic changes appear to happen on their own, without any clear cause.

Some epigenetic changes happen as a result of certain types of chemical reactions in the body. Even some genes contribute to epigenetic changes.

Cesarean Delivery May Cause Epigenetic Changes In Babies DNA Babies coming into the world by cesarean section experience epigenetic changes, a study has found. So far there has not been enough follow up to know whether the effects are long lasting, but the discovery may explain the relatively poorer outcomes for babies delivered in this way. Cesarean delivery, where the mother’s abdomen and uterus are surgically cut open to remove the baby, was once a last, desperate option. Studies found higher rates of methylation in stem cells from babies delivered by cesarean than via vaginal birth. Methylation of DNA affects whether genes are expressed or not within a cell and is the major path through which environmental factors can alter the expression of genetic traits.

Epigenetic Inheritance – It may be possible to pass down epigenetic changes to future generations if the changes occur in sperm or egg cells. Most epigenetic changes that occur in sperm and egg cells get erased when the two combine to form a fertilized egg, in a process called “reprogramming.” This reprogramming allows the cells of the fetus to “start from scratch” and make their own epigenetic changes. But scientists think some of the epigenetic changes in parents’ sperm and egg cells may avoid the reprogramming process, and make it through to the next generation. If this is true, things like the food a person eats before they conceive could affect their future child. However, this has not been proven in people.

Epigenetics and Diseases

Alterations in epigenetic pathways have been shown to be implicated in common human diseases

Common, chronic diseases of Western societies, such as eczema, asthma, diabetes, coronary heart disease, depression and cancers, are very different. They are nearly all multifactorial, so defining the cause is impossible. There are many contributing factors, including the person’s genetic makeup. Imagine driving along a narrow, winding country lane in the rain, having just had a row with your partner. The windscreen is fogged up, and your car has rather bald tyres. You round the corner to find the lane blocked by a tractor backing into a field, and crash into the tractor. . A few examples are given below to illustrate the importance of epigenetic pathways in disease development.

  • Epigenetic and Cancer – The first human disease to be linked to epigenetics was cancer, in 1983. Epigenetic changes have been observed in virtually every step of tumor development and progression. Too little DNA methylation (hypomethylation) is believed to initiate chromosome instability and activate oncogenes.

A malignant cell can have 20- 60% less genomic methylation than its normal counterpart. Conversely, too much DNA methylation (hypermethylation) may initiate the silencing of tumor suppressor genes. Medical researchers are evaluating epigenetic markers as a means for early cancer diagnosis and prediction of clinical outcome. Therapeutics based on epigenetic strategies are also being considered for cancer treatment and prevention. How epigenetic changes may be a mechanism of environmental chemical-induced cancers is being researched as well.

  • Epigenetics and Aging – DNA methylation decreases as cells age. Identical twins are epigenetically indistinguishable early in life, but have substantial differences in epigenetic markers with age. This observation suggests an important role by the environment in shaping the epigenome. It has been shown that the process of aging involves some epigenetic pathways that have been identified in the process of carcinogenesis.
  • Epigenitics and Mental Retardation – Fragile X syndrome is the most frequently inherited mental disability, particularly in males. Both sexes can be affected by this condition, but because males only have one X chromosome, one fragile X will impact them more severely. Indeed, fragile X syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females. People with this syndrome have severe intellectual disabilities, delayed verbal development, and “autistic-like” behavior. The syndrome is caused by an abnormality in the FMR1- fragile X mental retardation 1 gene. People who do not have fragile X syndrome have 6 to 50 repeats of the trinucleotide CGG in their FMR1 gene. Loss of this specific protein causes fragile X syndrome. Although a lot of attention has been given to the CGG expansion mutation as the cause of fragile X, the epigenetic change associated with FMR1 methylation is the real syndrome culprit.
  • Other human diseases – There is increasing evidence that epigenetic changes play a

critical role in the development of certain human diseases, such as, neurodevelopmental

disorders, cardiovascular diseases, type-2 diabetes, obesity and infertility.

Epigenetic Therapy

The use of drugs to correct epigenetic defects, is a new and rapidly developing area of pharmacology. Epigenetic therapy is a potentially very useful form of therapy because epigenetic defects, when compared to genetic defects, are thought to be more easily reversible with pharmacological intervention. In addition to holding promise as therapeutic agents, epigenetic drugs may also be able to prevent disease. However, epigenetic therapy has its limitations, such as the fact that both DNMT as well as HDAC inhibitors may activate oncogenes due to lack of specificity, resulting in accelerated tumor progression. The drugs include –

DNMT inhibitors (DNA demethylating drugs) – These drugs inhibit methylation of DNA by inhibiting the DNMTs. Most of the DNMT inhibitors presently available are not specific for any of the DNMTs. Inhibition of DNA methylation can be therapeutically useful in cancer where hypermethylation of promoter regions of genes is the most well established epigenetic change known to occur. DNMT inhibitors are also being investigated as a means to reactivate the methylated and silenced foetal haemoglobin gene in patients with thalassaemia and sickle cell anaemia in order to increase production of haemoglobin F, thereby helping in the correction of anaemia that characterizes these diseases. Some of these drugs such as zebularine and procaine are small molecule DNMT inhibitors.

Non-nucleoside analogue DNMT inhibitors – The myelotoxic effects of the nucleoside analogue inhibitors has encouraged the search for inhibitors of DNA methylation that are not incorporated into DNA because of structural differences from cytosine. These non-nucleoside analogue inhibitors are undergoing preclinical trials. Some of these drugs such as procainamide and procaine have the potential advantage as these have already been extensively used in clinical practice.

Antisense oligonucleotides – Antisense oligonucleotides are short, defined sequences of nucleotides that are complementary to mRNAs and hybridize with them and make them inactive, thereby blocking translation.

HDAC inhibitors (chromatin remodelling drugs) – These drugs inhibit HDACs, which along with HATs, help maintain the acetylation status of histones. The anticancer effects of these drugs are thought to be due to the accumulation of acetylated histones leading to the modulation of the transcription of specific genes whose expression causes inhibition of cancer cell growth. Some HDAC inhibitors such as suberoylanilide hydroxamic acid and depsipeptide have been undergoing. Some HDAC inhibitors such as suberoylanilide hydroxamic acid37 and depsipeptide38 have been undergoing.

 

Reference

http://www.nature.com/scitable/content/epigenetic-diseases-and-their-causes-and-symptoms-37397

http://science.howstuffworks.com/life/genetic/epigenetics2.htm

https://www.nichd.nih.gov/health/topics/epigenetics/conditioninfo/pages/risk.aspx

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780862/

http://www.whatisepigenetics.com/dna-methylation/2/

http://www.zymoresearch.com/learning-center/epigenetics/epigenetic-biomarkers-treatments

http://science.howstuffworks.com/life/genetic/epigenetics4.htm

http://www.iflscience.com/health-and-medicine/cesarean-delivery-may-cause-epigenetic-changes-babies-dna

http://onlinelibrary.wiley.com/doi/10.1002/047001153X.g103227/pdf

February 7, 2017

Ehlers-Danlos syndrome (EDS) is a genetic disorder in which the structure of connective tissue is abnormal due to a gene mutation. This results in abnormally fragile and hyper-extensible tissues throughout the body which can lead to a range of multi-systemic symptoms; the effect on the body is widespread and not limited to one body system.

People with Ehlers-Danlos features need to see a doctor who knows about this and other connective tissue disorders for an accurate diagnosis; often this will be a medical geneticist. It is very important that people with Ehlers-Danlos syndrome are diagnosed early so they can begin the right treatments to prevent serious complications. There are six major types of EDS. The different types of EDS are classified according to their manifestations of signs and symptoms. Each type of EDS is defined as a distinct disorder that “runs true” in a family. This means that an individual with Vascular Type EDS will not have a child with Classical Type EDS.

Some forms of Ehlers-Danlos syndrome, notably the vascular type and to a lesser extent the kyphoscoliosis and classical types, can involve serious and potentially life-threatening complications due to unpredictable tearing (rupture) of blood vessels. This rupture can cause internal bleeding, stroke, and shock. The vascular type of Ehlers-Danlos syndrome is also associated with an increased risk of organ rupture, including tearing of the intestine and rupture of the uterus (womb) during pregnancy. People with the kyphoscoliosis form of Ehlers-Danlos syndrome experience severe, progressive curvature of the spine that can interfere with breathing.

At this time, research statistics of EDS show the prevalence as 1 in 2,500 to 1 in 5,000 people. Recent clinical experience suggests EDS is more common. The condition is known to affect both males and females of all racial and ethnic backgrounds.

Types of EDS

There are several different types of Ehlers-Danlos syndrome, each with its own set of features and complications. The most common form of Ehlers-Danlos syndrome is Ehlers-Danlos Hypermobility Type. It is characterized by loose joints and chronic (long-term) joint pain. Other forms of Ehlers-Danlos syndrome can involve serious and potentially life-threatening complications. These include –

  • Vascular Ehlers-Danlos syndrome, which can cause blood vessels to tear (rupture) unpredictably. This can lead to internal bleeding, stroke, and shock. Vascular Ehlers-Danlos syndrome is also associated with an increased risk of organ rupture, including tearing of the intestine and rupture of the uterus (womb) during pregnancy.
  • Kyphoscoliosis form of Ehlers-Danlos syndrome, which is associated with severe, progressive curvature of the spine that can interfere with breathing.

Causes

EDS is, in most cases an inherited condition, while a minority of cases are not inherited (meaning that they occur via spontaneous gene mutations).

 

Defects in the following genes cause EDS. All of these genes provide instructions on how to assemble collagen — except for ADAMTS2, which provides instructions for making the proteins that work with collagen.

  • ADAMTS2
  • COL1A1
  • COL1A2
  • COL3A1
  • COL5A1
  • COL6A2
  • PLOD1
  • TNXB

Defects in these genes weaken the process and formation of collagen. Collagen is made up of molecules that give structure to connective tissues in the body.

Symptoms

The symptoms of EDS vary depending on the type of disorder, and can range from mild to life threatening. Some of the common symptoms include –

  • Hypermobility in the hands, fingers and toes
  • Loose joints that are prone to sprains, dislocations and double-jointedness
  • Flat feet
  • A high narrow palate with dental crowding
  • Pale, smooth skin that bruises easily
  • Skin that stretches easily
  • Wounds that don’t heal easily and with abnormal scarring
  • Hernias
  • Myalgia and arthralgia
  • Muscle weakness, especially when cold
  • Early onset osteoarthritis

Some of the less common symptoms include –

  • Low bone density
  • Scoliosis
  • Irritable bowel syndrome
  • Carpal tunnel syndrome
  • Hearing loss
  • Delayed motor skills in infants
  • Large eyes, small chin, thin nose and lips
  • Small stature

Complications

Possible complications of Ehlers-Danlos syndrome include –

  • Chronic joint pain
  • Early-onset arthritis
  • Failure of surgical wounds to close (or stitches tear out)
  • Premature rupture of membranes during pregnancy
  • Rupture of major vessels, including a ruptured aortic aneurysm (only in vascular EDS)
  • Rupture of a hollow organ such as the uterus or bowel (only in vascular EDS)
  • Rupture of the eyeball

Treatment

Current treatment options for EDS include –

  • Celiprolol, a beta 1-adrenoceptor antagonist with a beta 2-adrenoceptor agonist action, has been used to prevent arterial dissections and ruptures in patients with vascular EDS. It is thought to act via a reduction in vascular haemodynamic stress with exercise and/or through a reduction in transforming growth factor-b. Patients with EDS vascular type may also benefit from the surgical treatment of complications.[13]
  • Trauma should be minimised and protective clothing and padding may help. For patients with skin and soft tissue fragility, extra care (eg, non-tension sutures to skin, deep double sutures to other wounds, leaving stitches in for twice the normal time) should be taken when repairing injuries.
  • Children with hypotonia and delay in motor development should receive physiotherapy.
  • Physiotherapy will also be useful for adult patients with joint hypermobility problems. Anti-inflammatory tablets and analgesics may be required to control pain.
  • Ascorbic acid is sometimes recommended to lessen the risk of spontaneous bruising.
  • Genetic counselling should be provided.

Alternative Treatment

Magnesium is mandatory for regulation of synthesis and degradation of collagen and elastin, proteoglycans, and glycoproteins. Thus, since connective tissue is already the issue at hand in EDS, it is easy to understand how a deficiency of magnesium further negatively affects connective tissue health.

Vitamin C may help decrease bruising and aid in wound healing.

Methyl sulphonyl methane (MSM) and Silica is a combination supplement required by the body for the formation of bone, and collagen in connective tissue (cartilage, tendons, ligaments), and for healthy skin, hair and nails. MSM and silica help maintain the flexibility of joints and arteries, and inhibit the development of cardiovascular disease and osteoporosis.

Pycnogenol (from pine bark extract) is an alternative term for proanthrocyanidins, chemical substances belonging to one of the most beneficial groups of plant flavonoids. Pycnogenols decrease capillary permeability and fragility, and inhibit the development of venous insufficiency and varicose veins. Pycnogenol helps maintain the strength, flexibility and suppleness of skin.

Glucosamine is a sugar-related nutrient used within the body to form more complex molecules, which are necessary for the maintenance and repair of connective tissue and joints.

Carnitine is an amino acid like substance which is important in the metabolism of fat and energy production within the body, and promotes normal heart and skeletal muscle function. Carnitine supplements increase the tolerance of muscle to physical exercise, and help prevent exercise induced muscle pain and muscle weakness.

Coenzyme Q10 is a vitamin like substance which plays a key role in the body’s energy supply mechanisms, acting in conjunction with enzymes (hence the name coenzyme Q10) to convert sugars and fat into energy. Coenzyme Q10 promotes normal cardiovascular function, and has been used to counter the effects of cardiac mitral valve prolapsed.

Calcium is the most abundant mineral in the human body, and is responsible for maintaining healthy bones and teeth and inhibiting the development of osteoporosis. The skeleton acts as a reservoir for calcium; if the intake of calcium is insufficient, bones become depleted in calcium and osteoporosis develops.

Yoga and other stretching activities can also tighten and realign the body’s structure and relieve pain.

 

Reference –

http://www.merckmanuals.com/home/children’s-health-issues/hereditary-connective-tissue-disorders/ehlers-danlos-syndrome

https://umm.edu/health/medical/ency/articles/ehlersdanlos-syndrome

http://www.childrenshospital.org/conditions-and-treatments/conditions/ehlers-danlos-syndrome

https://www.cda-adc.ca/jcda/vol-67/issue-6/330.html

http://www.webmd.com/children/ehlers-danlos-syndrome-11063

http://www.medicinenet.com/ehlers-danlos_syndrome/article.htm

http://www.mayoclinic.org/diseases-conditions/ehlers-danlos-syndrome/basics/causes/con-20033656

http://emedicine.medscape.com/article/1114004-clinical

http://www.bmj.com/content/335/7617/448

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=285

http://www.omim.org/entry/130020

February 7, 2017

Down syndrome is a developmental genetic disorder disorder caused by an extra copy of chromosome 21. It is by far the most common and best known chromosomal disorder in humans and the most common cause of intellectual disability.

Our bodies are made up of millions of cells. In each cell there are 46 chromosomes. The DNA in our chromosomes determines how we develop. Down syndrome is caused when there is an extra chromosome. People with Down syndrome have 47 chromosomes in their cells instead of 46. They have an extra chromosome 21, which is why Down syndrome is also sometimes known as trisomy 21. The extra chromosome is associated with other conditions such as varying degrees of developmental delay and intellectual disability, characteristic facial features, and increased risk of certain health conditions. This extra copy changes how the baby’s body and brain develop, which can cause both mental and physical challenges for the baby. The degree of these conditions varies greatly from child to child.

These children often suffer from various physical ailments, including:

  • Recurrent vomiting
  • Failure to thrive
  • Recurrent infections of the upper respiratory tract, including ear infections
  • Bed wetting
  • Constipation
  • Sleep disturbances
  • Hyperactivity
  • Autism and emotional and neurologic ailments

People with Down syndrome often experience a gradual decline in thinking ability (cognition) as they age, usually starting around age 50. Down syndrome is also associated with an increased risk of developing Alzheimer disease, a brain disorder that results in a gradual loss of memory, judgment, and ability to function. Approximately half of adults with Down syndrome develop Alzheimer disease. Although Alzheimer disease is usually a disorder that occurs in older adults, people with Down syndrome usually develop this condition in their fifties or sixties.

Down syndrome, itself, does not have a cure. But, treatment is available for many of the symptoms and conditions that can accompany the diagnosis.

Types of Down Syndrome

There are three types of Down syndrome. People often can’t tell the difference between each type without looking at the chromosomes because the physical features and behaviors are similar.

Trisomy 21 – About 95% of people with Down syndrome have Trisomy 21.With this type of Down syndrome, each cell in the body has 3 separate copies of chromosome 21 instead of the usual 2 copies.

Translocation Down syndrome – This type accounts for a small percentage of people with Down syndrome (about 3%).This occurs when an extra part or a whole extra chromosome 21 is present, but it is attached or “trans-located” to a different chromosome rather than being a separate chromosome 21.

Mosaic Down syndrome – This type affects about 2% of the people with Down syndrome. Mosaic means mixture or combination. For children with mosaic Down syndrome, some of their cells have 3 copies of chromosome 21, but other cells have the typical two copies of chromosome 21. Children with mosaic Down syndrome may have the same features as other children with Down syndrome. However, they may have fewer features of the condition due to the presence of some (or many) cells with a typical number of chromosomes.

Causes

Down syndrome occurs in about 1 in 800 newborns. About 5,300 babies with Down syndrome are born in the United States each year, and an estimated 250,000 people in this country have the condition. Although women of any age can have a child with Down syndrome, the chance of having a child with this condition increases as a woman gets older.

Genetic – Down syndrome is typically caused by what is called nondisjunction. Nondisjunction happens when a pair of chromosomes fails to separate during egg (or sperm) formation. When that egg unites with a normal sperm to form an embryo, the embryo ends up with three copies of chromosome 21 instead of the normal two. The extra chromosome is then copied in every cell as the baby develops. Interestingly, nondisjunction events seem to occur more frequently in older women. This may explain why the risk of having a baby with Down syndrome is greater among mothers age 35 and older.

Risk Factors

Down syndrome occurs in people of all races and economic levels, though older women have an increased chance of having a child with Down syndrome. All 3 types of Down syndrome are genetic conditions (relating to the genes), but only 1% of all cases of Down syndrome have a hereditary component (passed from parent to child through the genes). Heridity is not a factor in trisomy 21 (nondisjunction) and mosaicism. However, in one third of cases of Down syndrome resultuing from translocation there is a heriditary compontent – accounting for about 1% of all cases of Down syndrome. The risk factors include –

Advancing maternal age – A woman’s chances of giving birth to a child with Down syndrome increase with age because older eggs have a greater risk of improper chromosome division. By age 35, a woman’s risk of conceiving a child with Down syndrome is about 1 in 350. By age 40, the risk is about 1 in 100, and by age 45, the risk is about 1 in 30. However, most children with Down syndrome are born to women under age 35 because younger women have far more babies.

Having had one child with Down syndrome – Typically, a woman who has one child with Down syndrome has about a 1 in 100 chance of having another child with Down syndrome.

Being carriers of the genetic translocation for Down syndrome – Both men and women can pass the genetic translocation for Down syndrome on to their children.

Metal Toxicity – Since mercury and other toxic metals destroys DNA, it’s possible that they may increase the risk for Down syndrome in few cases.

Symptoms

Down syndrome can affect a child physically, cognitively, and behaviorally. Remember that every child with the condition is unique and may possess these characteristics to different degrees or not at all.

Physical

A child with Down syndrome will have some, but perhaps not all, of the following features –

  • Eyes that slant upward, from inner corner to outer corner
  • Small ears that may fold over slightly at the top
  • A smaller than average mouth, and larger appearing tongue
  • A smaller than average nose, with a flattened nasal bridge
  • Short, stocky arms and legs. Some children also have a wide space between the big toe and second toe.
  • Some babies with Down syndrome have short necks and small hands with short fingers
  • One single crease that goes straight across the palm, and a second crease that curves down by the thumb, rather than having three creases in the palm of the hand
  • Shorter than average height
  • Low muscle tone (hypotonia) throughout the body and increased looseness or flexibility in the joints

Developmental, Cognitive, and Behavioral Symptoms

  • Most children with Down syndrome have delays in meeting developmental milestones. They typically learn to walk and talk at later times than children without Down syndrome.
  • Children with Down syndrome often have mild to moderate cognitive impairment and intellectual disability
  • Children with Down syndrome often have specific patterns of cognitive and behavioral features including –
    • Strengths in in social engagement and social behavior, visual learning, and word reading.
    • Challenges with attention span, verbal memory, and expressive communication.
  • Tailored and specialized educational programs and support enable children with Down syndrome to learn and grow at their own pace.
  • Behavioral problems such as stubborrness, impulsivity, and temper tantrums may be more common in children with Down syndrome
  • A child may use “self talk” (talking out loud to himself) as a way of understanding and processing information

Down syndrome is not a progressive condition. Therefore, symptoms do not get progressively worse over time. However, some of the complications associated with Down syndrome can occur at different stages in a child’s life.

Complications

Many people with Down syndrome have the common facial features and no other major birth defects. However, some people with Down syndrome might have one or more major birth defects or other medical problems. Some of the more common health problems among children with Down syndrome are –

  • Hearing loss (up to 75% of people with Down syndrome may be affected)
  • Obstructive sleep apnea, which is a condition where the person’s breathing temporarily stops while asleep (between 50 -75%)
  • Ear infections (between 50 -70%)
  • Eye diseases (up to 60%), like cataracts and eye issues requiring glasses
  • Heart defects present at birth (50%)

Other less common health problems among people with Down syndrome include –

  • Intestinal blockage at birth requiring surgery
  • Hip dislocation
  • Thyroid disease
  • Anemia (red blood cells can’t carry enough oxygen to the body) and iron deficiency (anemia where the red blood cells don’t have enough iron)
  • Leukemia in infancy or early childhood
  • Hirschsprung disease
  • Pulmonary hypertension, a condition that affects arteries in the heart and lungs, and which often resolves in the newborn period.
  • Atlantoaxial instability (cervical spine vertebrae may be more flexible causing a small but increased risk for spinal cord injury or compression).
  • Obesity/Overweight

Health care providers routinely monitor children with Down syndrome for these conditions. If they are diagnosed, treatment is available.

Treatment

There is no cure for Down syndrome. But physical therapy and/or speech therapy can help people with the disorder develop more normally. Screening for common medical problems associated with the disorder, followed by corrective surgery, can often improve quality of life. Moreover, enriched environments significantly increase children’s capacity to learn and lead meaningful lives.

When breast-feeding, the baby should be well supported and fully awake. The baby may have some leakage because of poor tongue control. However, many infants with Down syndrome can successfully breast-feed.

If the person has any heart defects or other heart problems, antibiotics may need to be prescribed to prevent a heart infection called endocarditis.

Special education and training is offered in most communities for children with delays in mental development. Speech therapy may help improve language skills. Physical therapy may teach movement skills. Occupational therapy may help with feeding and performing tasks. Mental health care can help both parents and the child manage mood or behavior problems. Special educators are also often needed.

Alternative & Complementary Treatment

Various traditional and alternative treatment methods for Down syndrome have been popular over the years including the use of pituitary extract, glutamic acid, thyroid hormone, 5-hydroxytryptophan, dimethyl sulfoxide (DMSO), dihydroepiandosterone, sicca cell therapy and growth hormone.

Physical therapy includes activities and exercises that help build motor skills, increase muscle strength, and improve posture and balance.

Speech-language therapy can help children with Down syndrome improve their communication skills and use language more effectively.

Occupational therapy helps find ways to adjust everyday tasks and conditions to match a person’s needs and abilities.

Emotional and behavioral therapies work to find useful responses to both desirable and undesirable behaviors. Children with Down syndrome may become frustrated because of difficulty communicating, may develop compulsive behaviors, and may have Attention Deficit Hyperactivity Disorder and other mental health issues. These types of therapists try to understand why a child is acting out, create ways and strategies for avoiding or preventing these situations from occurring, and teach better or more positive ways to respond to situations.

Vitamins – Deficiencies of vitamin A vitamin B12 and vitamin C in individuals with Down syndrome have been reported.

Minerals – A considerable number of studies have looked at the role of zinc in Down syndrome. Serum levels of zinc have been reported as below normal, as well as plasma levels and whole blood levels. One study, however, did not find a general deficiency.Whole blood levels and plasma levels of selenium have also been reported to be below normal in children and adults with Down syndrome.

Amino acids – Imbalances in amino acid levels have been claimed in adults with Down syndrome.

Probiotics – Probiotics Can Alleviate GI Problems Of Down’s Syndrome Patients.

Tryptophan, Serotonin, Melatonin – Down’s syndrome individuals frequently show low serum tryptophan levels. Whether this deficiency is primary (poor tryptophan absorption) or secondary (increased tryptophan catabolism) is not known. Regardless of the cause, low tryptophan levels impair protein synthesis (tryptophan is usually a rate-limiting amino acid) and decrease serotonin levels (tryptophan is the precursor to serotonin). Serotonin is the brain neurotransmitter that not only regulates emotional control and sleep quality, but helps influence carbohydrate feeding behavior. People with low serotonin levels tend to have carbohydrate cravings.

Glutamine and Arginine – One of the key ammonia-carrying molecules in the brain is glutamine, an amino acid which tends to accumulate in Down’s syndrome. Glutamine is made from glutamate (glutamic acid) by the addition of one ammonia molecule, and from alpha-ketoglutarate by the addition of two ammonia molecules. Due to the general overabundance of ammonia in Down’s syndrome, alpha-ketoglutarate is the ideal precursor to supplement the glutamate/glutamine pathways without increasing the ammonia burden.

Collagen – The collagen connection to Down’s syndrome is fairly obvious. Newborn infants and children exhibit extreme joint laxity. In addition, structural defects in the formation of the heart affect roughly half of all Down’s syndrome individuals. Of the dozen-plus collagen genes that have been discovered, two of them reside near the tip of the 21st chromosome.

 

Reference –

http://www.healthline.com/health/down-syndrome#Treatment7

http://www.downs-syndrome.org.uk/about-downs-syndrome/

http://www.superduperinc.com/handouts/pdf/116_Down_Syndrome.pdf

http://www.ndss.org/Global/Aging%20and%20Down%20Syndrome.pdf

https://umm.edu/health/medical/ency/articles/down-syndrome

http://www.childrenshospital.org/conditions-and-treatments/conditions/down-syndrome

https://www.worlddownsyndromeday.org/

http://learn.genetics.utah.edu/content/disorders/chromosomal/down/

https://www.genome.gov/19517824

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066992/

http://www.downs-syndrome.org.uk/about-downs-syndrome/

http://www.nhs.uk/Conditions/Downs-syndrome/Pages/Introduction.aspx

http://www.downsyndrome.org.au/what_is_down_syndrome.html