Last modified: 2014-04-03
Abstract
Background: Peroxisome biogenesis disorders (PBDs) may have variable clinical expression, from severe, lethal to mild phenotypes with progressive evolution. PBDs are caused by mutations in PEX genes, which encode proteins, called peroxins, involved in the assembly of the peroxisome.
Objectives: To report a patient heterozygous for two novel mutations in the PEX3 gene with less severe phenotypic expression than reported previously for PEX3 patients.
Case Report: A five years old boy, first child of unrelated parents, presented with psychomotor retardation, axial and peripheral muscular hypotonia and nephrocalcinosis at 3 months of life. He was born at term, and perinatal history was uneventful. At 18 months old he presented progressive spastic paraparesis, neurogenic bladder and nystagmus that evolved to bilateral cataract at 4 years old.
Methods: Peroxisomal parameters were studied in cultured skin fibroblasts. PEX genes were sequenced in DNA isolated from fibroblasts.
Results: Catalase immunofluorescence showed a peroxisomal mosaic pattern with all cells containing peroxisomal membrane structures. Immunoblotanalysis for acyl CoA oxidase and peroxisomal thiolase was normal.
Sequencing identified two heterozygous, pathogenic mutations in the PEX3 gene.
Conclusion: Our patient expands the clinical spectrum for PEX3 patients, because PEX3 mutations usually result in a severe, early lethal phenotype
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