[ novel mutation in PEX 26 gene in Zellweger syndrome: a case report]

ABSTRACT

Zellweger syndrome is the most severe phenotype of the peroxisome biogenesis disorders caused by mutations in PEX genes. PEX 1, 6 and 26 genes are most frequently implicated. Clinical phenotype can't predict the mutated gene. To report a novel mutation in the PEX 26 gene in infant with typical Zellweger syndrome. The infant was the second child to consanguineous parents; the 1st child was dead with neonatal hypotonia. At two month of age, we noted a severe hypotonia and growth failure, characteristic facial dysmorphic features and cryptorchidism. Sensorial investigations showed optic atrophy. Cerebral tomography revealed white matter hypodensity. Radiological examination revealed calcific stippling of the patellas. The clinical diagnosis was supported by measurement of plasma very-long-chain fatty acids, with elevated C240/C220, C260/C220 ratios and decreased docosanoic acid peak. The diagnosis was confirmed by dosage of DHAP-AT activity in fibroblasts which was very low. Ultrastructural examinations showed the presence of peroxisomal ghosts. Genetic analysis demonstrated a new mutation in PEX 26 gene.The death occurred at the age of 8 months of refractor epilepsy and apneas. The poor prognosis of ZS incites paediatricians to consider this disorder in etiological investigations of precocious hypotonia. Biochemical diagnosis, available in Tunisia, offers opportunity of prenatal diagnosis in affected families