The arylsulphatase A gene and molecular genetics of metachromatic leucodystrophy.

The lysosomal storage disorders share one common characteristic: the accumulation of a particular substrate inside the lysosome. Each disorder in this group is caused either by the deficiency of a lysosomal enzyme responsible for one step of the degradation pathway of a substrate, lack of a transporter involved in the movement of a small molecule across the lysosomal membrane, or absence of a low molecular weight activator protein required for in vivo hydrolysis of a sphingolipid. There are now more than 30 lysosomal storage diseases where the biochemical defect is well known and fully characterised. In this group, metachromatic leucodystrophy (MLD) is an autosomal recessive disorder that has been extensively studied over the past few decades.' The overall incidence of MLD is estimated to be 1:40 0002 and the enzymatic defect associated with this disease was discovered in the 1960s. More recently, the molecular biology of MLD has been elucidated, adding to the well established biochemical knowledge. Systematic mutation analyses have been carried out in an attempt to establish genotype-phenotype relationships. A clear understanding of the molecular basis of this disease will be helpful in the genetic counselling of affected families.