Metachromatic leucodystrophy (MLD) is a neurodegenerative lysosomal storage disease resulting from a deficiency of arylsulphatase A (EC 3.1.6.1), an enzyme involved in the normal catabolism of cerebroside sulphatide.1 The arylsulphatase A gene, located on chromosome 22, has a few common mutations that occur in a significant proportion of cases. Among these is P426L, sometimes known as the “A” or adult onset allele,2 which is associated with juvenile or adult onset MLD. Another less frequent mutation, A212V,3 is responsible for a more severe deficiency and has been identified in subjects of British, French, and Acadian descent.3 4 A pseudodeficiency allele also occurs in the arylsulphatase A gene, consisting of a glycosylation site mutation (N350S) and an A→G in the first poly A addition signal (AATAAC→AGTAAC). This pair of mutations has an allele frequency of up to 20% in the general population.5 6 The N350S mutation occurs alone in about 5% depending on ethnicity. Only one case of the poly A site mutation occurring alone has been documented.7

Subjects may have apparent mixtures of independent cell types at the level of a tissue or the whole body and may be described as mosaic or chimaeric. The distinction between mosaics and chimaeras has been recognised for some time.8 Cell lines of mosaics will have an underlying genetic identity and arise from events in chromosome duplication and cell division. In contrast, chimaeric cell lines are genetically distinct, arising from different zygotic lineages. We recently reported a family in Nova Scotia, Canada where a child with juvenile onset MLD carried A212V and P426L.3 We describe here a brother of the affected child, who is clinically well but apparently carries both A212V and P426L. The presence of additional genetic markers in the arylsulphatase A gene and elsewhere on …