[From gene to disease; Krabbe disease and galactosylceramidase deficiency]

Krabbe disease is a devastating lysosomal storage disease with autosomal recessive inheritance. Early symptoms of leukodystrophy, such as irritability and hypertonicity, appear at 3 to 6 months of age, but progress rapidly to severe mental and motor deterioration and death in the second year. The disease is caused by the deficiency of the lysosomal enzyme galactosylceramidase, which is in turn caused by mutations in the GALC gene. The incidence of the infantile form of the disease in the Netherlands is estimated at 1.3 per 100,000 births; 50% of the patients' alleles show the large 30-kb deletion. Early diagnosis by enzyme assay in leukocytes or skin fibroblasts permits timely genetic counselling and prenatal diagnosis, which is reliably made by enzyme or mutation analysis in the chorionic villi.