Novel mutations in the arylsulfatase A gene in eight Italian families with metachromatic leukodystrophy

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. We analysed the ARSA gene in eight unrelated Italian families with different clinical variants of MLD and identified three novel mutations: two Ser406Gly, (Glu329Ter) associated with late infantile MLD and one (Leu52Pro) with juvenile MLD. Only one family carried a pseudodeficiency allele (Asn350Ser). The IVS2 + 1G > A mutation occurred in four families. We also identified three polymorphisms, all in heterozygosis: Thr391Ser was present in five families, Trp193Cys in four families, and Ala210Ala in one family. We could identify 100% of the alleles causing MLD in the families, involving 12 different mutations, resulting in improved prognosis and genetic counselling.