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

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.