Krabbe disease or Globoid Cell Leukodystrophy (GLD) is a rare lysosomal disorder occurring in 1 in 100.000 newborns. An enzyme called beta-galactosylceramidase (GALC) which usually degrades toxic substances is not working in this disorder. Psychosines accumulate in the brain and in peripheral nerves and are toxic for myelinating cells. The by far most common form is the infantile form with first symptoms starting in early infancy, usually before the age of 6 months. Children suffering from this form usually deteriorate rapidly and die early. There are also forms with later onset, albeit these are much less frequent.
Later-onset forms are rare and are defined as onset after the first 18 to 24 months. These patients experience a progressive spastic paraparesis (stiff muscles, especially of the legs) and slow dementia. There is usually peripheral neuropathy.
The diagnosis of Krabbe disease is based on the typical clinical findings, typical MRI abnormalities and a undetectable or very low activity of galactocerebrosidase which can be measured in a bloodspot.
There is no established therapy for GLD. Hematopoietic stem cell transplantation (HSCT), often also called bone marrow transplantation, has been tried in all forms of the disease. If the infantile form has already become symptomatic, treatment is no longer possible as the disease process cannot be stopped once begun. If performed in the neonatal period before first symptoms have developed, HSCT cannot cure the disease. It is only able to modify the natural progression of the disease in children with the infantile form: children remain severely handicapped. All develop spasticity, many become microcephalic, only a minority is able to walk without support and a considerable number of transplanted children require gastrostomy for tube feeding. Mental development is also retarded. In most patients, these neurological symptoms are slowly progressive. In patients with late-onset disease, HSCT has been reported to stabilize the disease. Enzyme replacement therapy has not yet been studied in patients with Krabbe disease.
It is important to achieve comfort, and this is the main goal of therapy. Stiffness and irritability can be partly improved by medication, also epilepsy can be treated with drugs. All children with the early form will have feeding problems from quite early on and have to be fed via a nasogastric tube or a PEG.
Krabbe disease is genetic. It is inherited in an autosomal recessive manner and caused by mutations in the gene coding for beta-galactosylceramidase (GALC). This means that parents are healthy, but carry each one defective copy of the responsible gene. Click here for more information. If a child inherits two defective copies of this gene, it will be affected. Prenatal diagnosis is possible.
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