An Asn -> Lys substitution in saposin B involving a conserved amino acidicresidue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity

Sphingolipid activator proteins are small glycoproteins required for the de gradation of sphingolipids by specific lysosomal hydrolases. Four of them, called saposins, are encoded by the prosaposin gene, the product of which i s proteolytically cleaved into the four mature saposin proteins (saposins A , B, C, D). One of these, saposin B, is necessary in the hydrolysis of sulp hatide by arylsulphatase A where it presents the solubilised substrate to t he enzyme. As an alternative to arylsulphatase A deficiency, deficiency of saposin B causes metachromatic leukodystrophy, We identified a previously u ndescribed mutation (N215K) in the prosaposin gene of a patient,vith metach romatic leukodystrophy but with normal arylsulphatase A activity and elevat ed sulphatide in urine. The mutation involves a highly conserved amino acid ic residue and abolishes the only N-glycosylation site of saposin B.