Ethylmalonic and methylsuccinic aciduria in ethylmalonic encephalopathy arise from abnormal isoleucine metabolism.
Metabolism
; 47(7): 836-9, 1998 Jul.
Article
em En
| MEDLINE
| ID: mdl-9667231
ABSTRACT
Ethylmalonic encephalopathy (EE), an organic aciduria of unknown etiology characterized by developmental delay, hypotonia, and vascular instability associated with lactic acidemia and urinary excretion of ethylmalonic acid (EMA) and methylsuccinic acid (MSA), has been described in 11 patients. To test the possibility that the underlying biochemical defect involves isoleucine catabolism, we determined the response to oral L-isoleucine (IIe) load (150 mg/kg) in a 5-year-old girl with EE and in three healthy, age- and sex-matched controls. Following IIe load in the patient, there was accumulation of 2-methylbutyrylglycine (2-MBG) and a delayed and lower peak urinary excretion of tiglylglycine (TGL), suggesting a partial defect in 2-methyl-branched chain acylcoenzyme A dehydrogenase (2M-BCAD). In vitro measurements 2M-BCAD activity in cultured skin fibroblasts from patients with EE have been reported to be normal. Our results show that isoleucine is a source for the elevated EMA and MSA in patients with EE, and suggest a functional, possibly secondary, deficiency of activity of 2M-BCAD in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Succinatos
/
Encéfalo
/
Oxirredutases atuantes sobre Doadores de Grupo CH-CH
/
Isoleucina
/
Malonatos
/
Erros Inatos do Metabolismo
Limite:
Child, preschool
/
Female
/
Humans
Idioma:
En
Revista:
Metabolism
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Canadá