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

BackgroundHuman 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.ObjectivesWe 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.MethodsHistopathology, 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.ResultsHistopathology 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).LimitationsOnly one family was studied.ConclusionsA 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.