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

Vered Molho-Pessach, Ruth Bargal, Yigal Abramowitz, Victoria Doviner, Arieh Ingber, Annick Raas-Rothschild, Zvi Ne'eman, Marsha Zeigler, Abraham Zlotogorski

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Human β-mannosidosis, a rare disorder of oligosaccharide catabolism, results from a deficiency of β-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 β-mannosidase. Objectives: We report here a 36-year-old Arab female with β-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 β-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 β-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 β-mannosidosis and other lysosomal storage diseases is emphasized.

Original languageEnglish
Pages (from-to)407-412
Number of pages6
JournalJournal of the American Academy of Dermatology
Volume57
Issue number3
DOIs
StatePublished - Sep 2007
Externally publishedYes

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