Genetic screening for Krabbe disease: learning from the past and looking to the future.

In Israel, Krabbe disease is frequent in two Moslem Arab villages in the Jerusalem area. In this paper we present our experience of almost four decades with diagnosis of Krabbe disease, carrier screening and prenatal diagnosis. The screening program is well accepted by the community, and there is a clear trend towards premarital testing. The screening program and prenatal diagnosis have led to a decrease in the incidence of Krabbe disease from 1.6 per 1,000 live births to 0.82 per 1,000.

A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans.

A six-month-old infant girl presenting with progressive encephalopathy and abnormal myelination in the cerebral white matter was originally diagnosed as suffering from Krabbe disease. The diagnosis was based on a deficiency of galactocerebrosidase activity found in leukocytes isolated from whole blood. When cultured skin fibroblasts did not show a similar enzyme deficiency and sulphatide (stearoyl-1-14C) uptake indicated an abnormal storage of galactosylceramide, a deficiency of an activator was implied. A three base pair deletion was found in the saposin A coding sequence of the prosaposin gene leading to the deletion of a conserved valine at amino acid number 11 of the saposin A protein. This deletion in saposin A is proposed as the cause for the abnormal galactosylceramide metabolism in this infant. This is the first report of a saposin A mutation in humans leading to pathological consequences.