Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy

Hum Mutat. 2016 Jan;37(1):16-27. doi: 10.1002/humu.22919. Epub 2015 Nov 4.


Metachromatic leukodystrophy is a neurodegenerative disorder characterized by progressive demyelination. The disease is caused by variants in the ARSA gene, which codes for the lysosomal enzyme arylsulfatase A, or, more rarely, in the PSAP gene, which codes for the activator protein saposin B. In this Mutation Update, an extensive review of all the ARSA- and PSAP-causative variants published in the literature to date, accounting for a total of 200 ARSA and 10 PSAP allele types, is presented. The detailed ARSA and PSAP variant lists are freely available on the Leiden Online Variation Database (LOVD) platform at and, respectively.

Keywords: ARSA; PSAP; arylsulfatase A; metachromatic leukodystrophy; mutation; saposin B.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Cerebroside-Sulfatase / genetics*
  • Databases, Genetic
  • Genetic Association Studies*
  • Genotype
  • Humans
  • Leukodystrophy, Metachromatic / diagnosis
  • Leukodystrophy, Metachromatic / genetics*
  • Mutation*
  • Phenotype
  • Saposins / genetics*


  • PSAP protein, human
  • Saposins
  • Cerebroside-Sulfatase