Gaucher Disease

February 2, 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.


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).


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.



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


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 –

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