RESUMO
Fetal abnormalities including chylous ascites, polyhydramnios, claw hands, and hammer toes were identified in an infant who had a missense mutation R106P and a 52bp deletion in the gene for a peroxisomal beta-oxidation enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase, D-bifunctional protein. The patient had psychomotor retardation and craniofacial dysmorphism and died at 7 months of age. The patient had atypical fetal manifestations of this enzyme deficiency.
Assuntos
17-Hidroxiesteroide Desidrogenases , 3-Hidroxiacil-CoA Desidrogenases/deficiência , Ascite Quilosa/congênito , Ascite Quilosa/complicações , Contratura/congênito , Contratura/complicações , Enoil-CoA Hidratase , Deformidades Congênitas do Pé/complicações , Deformidades Congênitas da Mão/complicações , Hidroliases/deficiência , Complexos Multienzimáticos/deficiência , Poli-Hidrâmnios/complicações , 3-Hidroxiacil-CoA Desidrogenases/genética , Ascite Quilosa/genética , Contratura/genética , Evolução Fatal , Feminino , Deformidades Congênitas do Pé/genética , Deleção de Genes , Deformidades Congênitas da Mão/genética , Humanos , Hidroliases/genética , Lactente , Recém-Nascido , Masculino , Complexos Multienzimáticos/genética , Mutação de Sentido Incorreto/genética , Proteína Multifuncional do Peroxissomo-2 , GravidezRESUMO
We describe the clinical, pathologic, and biochemical findings for two peroxisome-deficient patients in a newly identified complementation group. Both patients had biochemical findings typical of patients with peroxisome biogenesis disorders. However, whereas one patient had the typical clinicopathologic features of Zellweger syndrome, the other patient's phenotype was atypical.
Assuntos
Catalase/química , Microcorpos/química , Microcorpos/genética , Transtornos Peroxissômicos/diagnóstico , Transtornos Peroxissômicos/genética , Fusão Celular , Consanguinidade , Fibroblastos/química , Teste de Complementação Genética , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Plasma , Síndrome de Zellweger/diagnóstico , Síndrome de Zellweger/genéticaRESUMO
A male infant with typical clinical and biochemical findings of Zellweger syndrome, but in whom hepatic peroxisomes were detected by electron microscopy, had profound hypotonia, hepatomegaly, typical facial appearance including large fontanelle and frontal bossing, convulsions, panaminoaciduria, and hyperammonemia. He died of liver failure at age 5 months. There were increased levels of very long chain fatty acids and trihydroxycoprostanic acid in serum, and increased excretion of dicarboxylic acids and tyrosine metabolites in the urine. Levels of peroxisomal enzymes, acyl coenzyme A oxidase, bifunctional protein, 3-ketoacyl coenzyme A thiolase, and dihydroxyacetone phosphate acyltransferase in the liver tissue from the patient were all deficient, findings consistent with Zellweger syndrome. However, immunocytochemical study and electron microscopic examination of the liver at autopsy revealed that hepatic peroxisomes were present at a level similar to that in a control subject. These observations suggest further heterogeneity in Zellweger syndrome and a different pathogenesis in this variant case.