Krabbe disease is also known by many other names, these include Globoid cell leukodystrophy, Galactosylcerebrosidase deficiency and Galactosylceramidase deficiency. It is a very rare condition that is caused by a genetic defect that affects the nervous system.
Those affected by Krabbe typically appear healthy until onset, or when an individual experiences symptoms, of the disease. Onset can vary from the first few weeks or months of life (Early Infantile Onset) into adulthood (Adult Onset).
Those who suffer from Krabbe Disease have a deficiency of an important enzyme called Galactosylceramidase (GALC).
Krabbe Disease is both a Leukodystrophy and Lysosomal Storage Disorder (LSD). Leukodystrophies are characterized as degenerative diseases of the white matter of the brain. LSDs occur when a part of the cell, called the lysosome, does not function properly. In a healthy individual, enzymes break down material in the lysosomes, however, if the body does not produce enough of a specific enzyme (ex: GALC), material builds up and becomes toxic.
Krabbe disease is divided into four subtypes based on when the disease begins:
- Type 1 – Infantile: begins at age 3 – 6 months
- Type 2 – Late infantile: begins at age 6 months – 3 years
- Type 3 – Juvenile: begins at age 3 – 8 years
- Type 4 – Adult onset: begins any time after 8 years of age
Krabbe Disease affects both the central and peripheral nervous systems, which are responsible for all of the body’s voluntary and involuntary movements. The central nervous system is made up of the nerves within the brain and spinal cord and is the primary control center of the body. The peripheral nervous system’s primary function is to carry information from the brain and spinal cord throughout the body to the limbs and organs.
Causes
Krabbe disease is an autosomal recessive disease caused by mutations in the GALC gene. An individual who inherits one copy of a GALC mutation is a “carrier” and is not expected to have related health problems. An individual who inherits two disease-causing mutations in this gene, one from each parent, is expected to be affected with Krabbe disease.
If both members of a couple are carriers, the risk for an affected child is 25% in each pregnancy; therefore, it is especially important that the reproductive partner of a carrier be offered testing.
A defect in the GALC gene causes Krabbe disease. Persons with this gene defect do not make enough of a substance called galactocerebroside beta-galactosidase (galactosylceramidase). The body needs this substance to make myelin, the material that surrounds and protects nerve fibers. Without it, myelin breaks down, brain cells die, and nerves in the brain and other body areas do not work properly.
This condition is very rare. It is most common among people of Scandinavian descent.
Risk Factors
Krabbe disease can occur in individuals of all races and ethnicities, but it occurs most commonly among Muslim Arabs and Druze communities in Israel. The incidence is estimated to be 1 in 100,000 in the United States and Europe, with a calculated carrier frequency of 1 in 158.3
Having a relative who is a carrier or who is affected can increase an individual’s risk of being a carrier. Consultation with a genetics health professional may be helpful in determining carrier risk and appropriate testing.
Symptoms
The majority of cases of Krabbe Disease appear within the first year of life. The patients rapidly regress to a condition with little to no brain function, and generally die by age 2, though some have lived longer. Death generally occurs as a result of a respiratory infection or brain fever. Symptoms that might be encountered in the infantile form of Krabbe Disease include –
- Developmental delay
- Seizures
- Limb stiffness
- Optic atrophy: wasting of a muscle of the eye, resulting in vision diffculties
- Neurosensoral deafness
- Extreme irritability
- Spasticity – presence of spasms
- Ataxia – loss of the ability to control muscular movement
- Progressive psychomotor decline: progressive decline in the coordination of movement
Although the majority of Krabbe Disease patients show symptoms within the first year of life, there have been cases diagnosed at all ages, through late adulthood. In general, the earlier the diagnosis, the more rapid the progression of the disease. Those who first show symptoms at ages 2-14 will regress and become severely incapacitated, and generally die 2-7 years following diagnosis. Some patients who have been diagnosed in the adolescent and adult years have symptoms that remain confined to weakness without any intellectual deterioration, while others may become bedridden and deteriorate both mentally and physically.
Complications
This disease damages the central nervous system. It can cause –
- Blindness
- Deafness
- Severe problems with muscle tone
The disease is usually life-threatening.
Treatment
Bone marrow transplantation and umbilical cord blood stem cell transplant are the ecognized treatments and have been found to preserve cognitive functions in some cases.
Anticonvulsant medications to manage seizures
Drugs to ease muscle spasticity and irritability
Physical therapy to minimize deterioration of muscle tone
Nutritional support, such as the use of a tube to deliver fluids and nutrients directly into the stomach (gastric tube)
Reference –
http://www.babysfirsttest.org/newborn-screening/conditions/krabbe
http://www.tloaf.org/krabbe.html
http://www.omim.org/entry/245200
https://rarediseases.info.nih.gov/gard/6844/krabbe-disease/resources/1
https://umm.edu/health/medical/ency/articles/krabbe-disease
http://www.wadsworth.org/newborn-screening/krabbe-disease
http://www.wadsworth.org/newborn-screening/krabbe-disease