Krabbe Disease (Globoid cell leukodystrophy)

What is Krabbe Disease?

In Krabbe disease, there is a lack of an enzyme called galactosylceramide beta-galactosidase (GALC); this enzyme breaks down several important compounds in the body. Without enough GALC, substances which should be broken down start to accumulate. The build-up of these substances damages the nerve cells in the central nervous system, destroying many of them and preventing the repair of others. This can result in neurological problems such as blindness, abnormal muscle tone and seizures.

Statistics on Krabbe Disease?

Krabbe disease is rare and is thought to affect 1 person in every 100,000 people in the general population. However, there is an unusually high incidence, 6 cases per 1000 live births in the Druze community in Israel.

Risk Factors for Krabbe Disease

As Krabbe's disease is inherited as an autosomal recessive trait the only known predisposing factor is having two parents who are carriers for the disorder.

Most reported cases have been among people of European ancestry.

Progression of Krabbe Disease

There are four clinical forms of Krabbe's disease, based on when symptoms of the disease occur.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 There is progressive damage to the central and peripheral nervous systems resulting in weakness, abnormal muscle tone, immobility, blindness, deafness,and seizures. Complications of this include infection and respiratory failure which are responsible for most deaths.

How is Krabbe Disease Diagnosed?

Galactocerebroside beta-galactosidase levels (levels can be measured from the serum, white blood cells, chorionic villi, and fibroblasts).

CSF total protein may be increased

MRI of the head is the best test to reveal abnormal white matter of the brain

CT of the head

Nerve conduction velocity showing delayed nerve conduction and evidence of demyelination

Presence of abnormal Globoid cells in biopsy tissue of the nervous system

Genetic testing may be available for the glycosylceramidase gene (GALC)

Prognosis of Krabbe Disease

Prognosis is generally poor, but varies depending on the subtype of disease. Most patients with the infantile and late infantile forms of Krabbe's disease will die within 2 years of disease onset. In the juvenile and adult forms disease may not be as severe, and life expectancy may be improved.

How is Krabbe Disease Treated?

There is no specific treatment for Krabbe disease. Bone marrow transplantation (with its own risks) has been attempted in early stages of the disease. It is too early to know if the new bone marrow can fully restore the brain to health in the small number of patients who have had this treatment.In the future there may be 'enzyme replacement therapy', but it is in the early stages of development as of 2003. Prevention by prenatal or genetic testing is available.Genetic counseling is recommended for prospective parents with a family history of Krabbe disease. Whether you are a carrier for the disease can be determined by testing your white blood cells or skin cells for decreased galactocerebroside beta-galactosidase levels. Prenatal diagnosis is possible by measuring galactocerebroside beta-galactosidase levels in cultured amniotic fluid cells or from cultured chorionic villi cells.

Krabbe Disease References

[1] Austin JH, Lehfeldt D: Studies in globoid (Krabbe) leucodystrophy. III Significance of experimentally produced globoid-like elements in rat white matter and spleen. J Neuropathol Exp Neurol 1965; 24: 265. [2] Dunn HG, Lake BD, Dolman CL, Wilson J: The neuropathy of Krabbe's infantile cerebral sclerosis (globoid cell leucodystrophy). Brain 1969; 92(2): 329-44[3] eMedicine[4] Farrell DF, Percy AK, Kaback MM, McKhann GM: Globoid cell (Krabbe's) leukodystrophy: heterozygote detection in cultured skin fibroblasts. Am J Hum Genet 1973 Nov; 25(6): 604-9[5] Hankey G., Wardlaw J. Clinical Neurology. Demos Medical Publishing, United Kingdom, 2002. [6] Medline Plus