LATE INFANTILE METACHROMATIC LEUKODYSTROPHY IN ISRAEL

Metachromatic Leukodystrophy (MLD) is a neurodegenerative disease in w hich the lysosomal enzyme, Aryl sulfatase A (ARSA) is deficient. The d isease is inherited as an autosomal recessive trait and its frequency is estimated to be 1/40,000 live births. The gene of ARSA has been clo ned and up to now eight mutations causing MLD have been reported. Anot her mutation, PD, leads to the deficiency of the enzyme in vitro (pseu dodeficiency) without any known clinical effect. The PD mutation is fr equent in all populations. In Israel, late infantile MLD was found to be very frequent in a small Jewish isolate, the Habbanite Jews (1/75 l ive births). The molecular analysis demonstrated that in the Habbanite population, the mutation occurred on an allele with the PD mutation. The loss of ARSA activity is due to a point mutation C > T leading to a change of proline to leucine. MLD is also frequent among Moslem Arab s in Jerusalem. The mutation is a transition G > A destroying the spli ce donor site of exon 2. This mutation has been reported in patients w ith the late infantile MLD from different ethnic groups. The Christian Arabs in Israel also have a high incidence of the disease (1/10,000 l ive births); the mutation in this population is still unknown. Knowled ge of the different mutations causing MLD in these defined populations will allow a carrier screening program to be carried out and prevent the birth of additional affected children.