Peroxisomal biogenesis disorders (PBD) are groups of inherited neurometabolic disorders caused by defects in PEX genes. We report on a female infant, born to a consanguineous parents (first degree cousins), who presented with inactivity, poor sucking, and
hypotonia early in the neonatal period. She had subtle dysmorphic features. Liver function tests were impaired with raised liver
enzymes, conjugated and unconjugated
hyperbilirubinemia. CT of the brain showed diffuse bilateral changes. She developed
seizures with an abnormal EEG. Plasma very long chain
fatty acid analysis showed high C26:0 levels and increasedC26:0/C22:0 and C24:0/C22:0 ratios, which is consistent with a PBD. Studies in fibroblasts including
plasmalogen biosynthesis, peroxisomal
fatty acid alfa and beta oxidation confirmed the diagnosis of PBD. Immunofluoresence microscopy revealed the absence of peroxisomes in fibroblasts. The patient was assigned to the PEX19 complementation group. Subsequent mutation analysis of the PEX19 gene revealed homozygosity for a c.320delA frameshift mutation. The patient had a stormy course with multiple admissions to the pediatric intensive care unit with
pneumonia, liver impairment,
sepsis, and
epilepsy. At 1 year of age she developed
metabolic acidosis with normal anion gap,
proteinuria, aminoaciduria, and glucosuria consistent with a renal tubular defect. Abdominal ultrasound showed multiple
gallstones. Other causes of
gallstones like haemoglobinopathy were excluded. So far, only two siblings had been reported with mutations in the PEX19 gene. Our patient showed a previously unrecognized association of
gallstones and a renal tubular defect with a PBD.