Screening for Krabbe disease: The first 2 years' experience

Globoid cell leukodystrophy or Krabbe disease is an autosomal recessive lysosomal storage disorder characterized by a deficiency in galactosylceramidase (GALC) which hydrolyses galactosylceramide and galactosylsphingosine (psychosine). The accumulation of psychosine results in the apoptosis of myelin-forming cells. The goals of this research were to identify the heterozygous carriers of Krabbe disease in Sicily (Italy), to prevent the birth of foetuses affected by this disease, and eventually in the presence of positive embryos to direct them towards a treatment before symptoms occur when it is too late to receive a useful therapy.

Since more than 100 mutations have been reported as a cause of Krabbe disease, we started to screen relatives of the affected patients, whose mutation was known. We used a fast, sensitive and painless assay extracting genomic DNA from buccal swabs. The genotypes of single-nucleotide polymorphisms (SNPs) were analysed to identify the carriers of the selected mutations.

In the last 2 years, we conducted the analysis of almost 100 subjects and individuated 40 heterozygotes carriers of Krabbe disease. One of the women examined was pregnant.

The knowledge obtained from our investigations provided and will provide notable practical benefit to families in which the disease is manifested and to researchers who deal with this rare pathology. Finally, the results of our study will be useful to know the real incidence of Krabbe disease in a large territory where it is particularly present and to start a Krabbe's register, which at present does not exist.