Krabbe disease or globoid cell leukodystrophy is an autosomal recessive disease caused by a deficiency in galactosylceramidase (or galactocerebrosidase), a lysosomal enzyme involved in the catabolism of a major lipid component of myelin.
The frequency seems to be 1 / 150,000 births in France.
The disease leads to demyelination of the central and peripheral nervous system. The early disappearance of oligodendrocytes appears to be due to the accumulation of a cytotoxic metabolite (galactosylsphingosine or “psychosine”).
In a majority of cases, it begins during the first year of life and is rapidly progressive. However, a later onset in children, adolescents or adults, is possible, with varying duration of development.
Forms of the disease
The ’classic’ infantile form represents 85 to 90% of cases. The initial symptoms are increasing irritability with hypertonia and hyperesthesia, and signs of peripheral neuropathy. Subsequently, hypertonic crises with opisthotonos are frequent; seizures may appear. At a more advanced stage, blindness and deafness appear, followed by vegetative state and finally hypotonia.
In late-onset forms, the first signs are often gait disturbances (spastic paraparesis or ataxia), hemiplegia, deterioration of vision, with or without peripheral neuropathy. Mental deterioration is variable (generally absent in adult forms).
The galactosylceramidase gene, located at 14q31, has been identified. Two mutations are more frequent (65% of alleles in France). Diagnostic.
The diagnosis of the disease remains enzymatic (activity of galactosylceramidase).