TY - JOUR
T1 - A Mutation in PEX19 Causes a Severe Clinical Phenotype in a Patient With Peroxisomal Biogenesis Disorder
AU - Mohamed, Sarar
AU - El-Meleagy, Ebtisam
AU - Nasr, Abdelhaleem
AU - Ebberink, Merel S.
AU - Wanders, Ronald J. A.
AU - Waterham, Hans R.
PY - 2010
Y1 - 2010
N2 - 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. (C) 2010 Wiley-Liss, Inc
AB - 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. (C) 2010 Wiley-Liss, Inc
U2 - https://doi.org/10.1002/ajmg.a.33560
DO - https://doi.org/10.1002/ajmg.a.33560
M3 - Article
C2 - 20683989
SN - 1552-4825
VL - 152A
SP - 2318
EP - 2321
JO - American journal of medical genetics. Part A
JF - American journal of medical genetics. Part A
IS - 9
ER -