Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation

J Am Acad Dermatol. 2007 Sep;57(3):407-12. doi: 10.1016/j.jaad.2007.01.037. Epub 2007 Apr 8.

Abstract

Background: Human beta-mannosidosis, a rare disorder of oligosaccharide catabolism, results from a deficiency of beta-mannosidase activity. So far, mutational analysis has been performed in only seven families and revealed 11 mutations in the MANBA gene which encodes the enzyme beta-mannosidase.

Objectives: We report here a 36-year-old Arab female with beta-mannosidosis who presented with mental retardation and multiple angiokeratomas. We describe in this patient a novel null mutation and review the previously reported MANBA gene mutations and their clinical correlations.

Methods: Histopathology, ultrastructural analysis, and enzyme assays were performed. Sequencing of cDNA and genomic DNA analysis was conducted in a search for a mutation in the MANBA gene.

Results: Histopathology of a skin biopsy specimen from the patient showed the characteristic findings of angiokeratoma. Electron microscopy showed cytoplasmic vacuolation. Enzymatic activity of beta-mannosidase in the patient's serum, leukocytes, and fibroblasts was less than 1% of control values. Sequencing of the MANBA cDNA revealed a G-->A transition in exon 6 at nucleotide position c.693, resulting in the formation of a stop codon (W231X).

Limitations: Only one family was studied.

Conclusions: A new case of human beta-mannosidosis is presented and the first MANBA gene mutation from Arab ancestry is reported. Reviewing the reported MANBA gene mutations does not reveal a clear genotype-phenotype correlation. The importance of angiokeratoma corporis diffusum as the clue to the diagnosis of beta-mannosidosis and other lysosomal storage diseases is emphasized.

Publication types

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

MeSH terms

  • Adenine
  • Adult
  • Arabs / genetics*
  • Base Sequence
  • Codon, Nonsense*
  • Codon, Terminator
  • Cytoplasm / ultrastructure
  • Exons
  • Fabry Disease / etiology*
  • Fabry Disease / pathology
  • Female
  • Guanine
  • Humans
  • Microscopy, Electron
  • Molecular Sequence Data
  • Skin / pathology
  • Vacuoles / ultrastructure
  • beta-Mannosidase / genetics*
  • beta-Mannosidosis / complications*
  • beta-Mannosidosis / genetics*

Substances

  • Codon, Nonsense
  • Codon, Terminator
  • Guanine
  • beta-Mannosidase
  • Adenine