Abstract

Metachromatic leucodystrophy (MLD) is an autosomal recessive lysosomal storage disease resulting from a severe deficiency of arylsulphatase A. The arylsulphatase A gene is located on chromosome 22 at q13.3. An MLD patient is described who carries a common splicing mutation (“I” allele) and a de novo ring 22 deleted for the arylsulphatase A gene. The fatehr was determined to be a heterozygous carrier of the “I” allele and the mother a heterozygous carrier of the arylsulphatase A pseudodeficiency allele. The ring 22 was shown by Southern blotting to be deleted in one copy of the arylsulphatase A gene. Minisatellite analysis showed the extent of the deletion and confirmed the biparental inheritance of chromosome 22 sequences. The carrier status of the parents and the patient's 46,XX,r(22) karyotype complicated the initial diagnosis in this family. However, the causal relationship of the ring 22 and MLD have implications for the recurrence risk in this family.