Skip to main content
SpringerLink
Log in

Pseudodeficiency of arylsulphatase A: Strategy for clarification of genotype in families of subjects with low ASA activity and neurological symptoms

  • Published:
Journal of Inherited Metabolic Disease

Summary

A benign deficiency (pseudodeficiency) of the lysosomal enzyme arylsulphatase A (ASA) (EC 3.1.6.8) towards synthetic substrates complicates the diagnosis of metachromatic leukodystrophy (MLD). The pseudodeficiency is due to a single base substitution in the 3′-untranslated region of the ASA gene (1524+95 A→G) and it has been reported that this mutation (PD2) always occurs on a chromosome carrying a second mutation in the ASA gene (PD1), which abolishes anN-glycosylation site (N350S). Analysis of the two PD mutations in the ASA gene separately was carried out in a large group of subjects with neurological symptoms and low ASA activity, including close relatives and MLD patients. The relationship between ASA enzyme activity and the different genotypes identified is presented. Evidence for the existence of an allele containing the PD2 mutation alone is presented. A strategy for cases with low ASA activity and neurological symptoms in families carrying a PD allele or both PD and MLD alleles is proposed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Barth ML, Ward C, Harris A, Saad A, Fenson A (1994) Frequency of arylsulphatase A pseudodeficiency-associated mutations in a healthy population.J Med Genet 31: 667–671.

    Article  PubMed  CAS  Google Scholar 

  • Davies JP, Winchester BG, Malcolm S (1993) Sequence variations in the first exon of α-galactosidase A.J Med Genet 30: 658–663.

    PubMed  CAS  Google Scholar 

  • Gieselmann V (1991) An assay for the rapid detection of the arylsulfatase A pseudodeficiency allele facilitates diagnosis and genetic counselling for metachromatic leukodystrophy.Hum Genet 86: 251–255.

    Article  PubMed  CAS  Google Scholar 

  • Gieselmann V, Polten A, Kreysing J, von Figura K (1989) Arylsulfatase A pseudodeficiency: loss of a polyadenylation signal andN-glycosylation site.Proc Natl Acad Sci USA 86: 9436–9440.

    Article  PubMed  CAS  Google Scholar 

  • Goldenfum S, Malcolm S, Young E, Winchester B (1993) The molecular detection of the pseudodeficiency allele for arylsuphatase A in patients with neurological symptoms and low arylsulphatase A activity.J Inher Metab Dis 16: 1048–1049.

    Article  PubMed  CAS  Google Scholar 

  • Hohenschutz C, Eich P, Friedl W, Waheed A, Conzelmann E, Propping P (1989) Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications.Hum Genet 82: 45–48.

    Article  PubMed  CAS  Google Scholar 

  • Kihara H, Chen-Kung H, Fluharty AL, Tsay KK, Hartlage PL (1980) Prenatal diagnosis of metachromatic leukodystrophy in a family with pseudoarylsulfatase A deficiency by the cerebroside sulfate loading test.Pediatr Res 14: 224–227.

    PubMed  CAS  Google Scholar 

  • Kolodny EH, Fluharty AL (1995) Metachromatic leukodystrophy and multiple sulfatase deficiency: sulfatide lipidosis. In Scriver CR, Beaudet AL, Sly AL, Valle D, eds.The Metabolic and Molecular Bases of Inherited Disease, 7th edn. New York: McGraw-Hill, 2693–2739.

    Google Scholar 

  • Kudoh T, Wenger DA (1982) Diagnosis of MLD, Krabbe disease, and Farber disease after uptake of fatty acid-labeled cerebroside sulfate into cultured skin fibroblasts.J Clin Invest. 70: 89–97.

    Article  PubMed  CAS  Google Scholar 

  • Lee-Vaupel M, Conzelmann E (1987) A simple chromogenic assay for arylsulphatase A.Clin Chim Acta 164: 171–180.

    Article  PubMed  CAS  Google Scholar 

  • Miller SA (1988) A simple salting out procedure for extracting DNA from human nucleated cells.Nucleic Acids Res 16: 1215.

    PubMed  CAS  Google Scholar 

  • Nelson PV, Carey WF, Morris CP (1991) Population frequency of the arylsulfatase A pseudodeficiency allele.Hum Genet 87: 87–88.

    Article  PubMed  CAS  Google Scholar 

  • Salamon MB, Christensen E, Schwartz M (1994) Searching for mutations in the arylsulphatase A gene.J Inher Metab Dis 17: 311–314.

    Article  PubMed  CAS  Google Scholar 

  • Shen N, Li ZG, Waye JS, Francis G, Chang PL (1993) Complications in the genotypic molecular diagnosis of pseudo arylsulfatase A deficiency.Am J Med Genet 45: 631–637.

    Article  PubMed  CAS  Google Scholar 

  • Zlotogora J, Furman-Shaharabani Y, Goldenfum S, Winchester B, von Figura K, Gieselmann V (1994) Arylsulfatase A pseudodeficiency: a common polymorphism which is associated with a unique haplotype.Am J Med Genet 52: 146–150.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biochemistry and Genetics, Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK

    S. Leistner, E. Young, C. Meaney & B. Winchester

Authors
  1. S. Leistner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Meaney
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Winchester
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leistner, S., Young, E., Meaney, C. et al. Pseudodeficiency of arylsulphatase A: Strategy for clarification of genotype in families of subjects with low ASA activity and neurological symptoms. J Inherit Metab Dis 18, 710–716 (1995). https://doi.org/10.1007/BF02436761

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02436761

Keywords

Search

Navigation