Identification of novel mutations of the HADHA and HADHB genes in patients with mitochondrial trifunctional protein deficiency.
Int J Mol Med
; 19(1): 81-7, 2007 Jan.
Article
em En
| MEDLINE
| ID: mdl-17143551
ABSTRACT
Patients with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency manifest hypoketotic hypoglycemia, hepatomegaly, hypotonia, lactic acidemia, acute renal failure, cardiomyopathy, and sudden death. We describe four novel mutations of the alpha- and beta-subunits of the mitochondrial trifunctional protein in four patients from three unrelated families. Their plasma acylcarnitine profiles suggested the presence of LCHAD deficiency by demonstrating highly elevated 3-hydroxyacyl carnitines by tandem mass spectrometry (MS/MS). Patients 1 and 2 had siblings who had died of lactic acidemia during the neonatal period. These patients also manifested lactic acidemia and died in the neonatal period. Patient 3 had a family history of Reye-like syndrome. She exhibited acute renal failure, rhabdomyolysis, pericardial effusion, and myopathy at the age of 12 years. DNA analysis of patients 1 and 2 revealed homozygosity for a c.1689+2T>G mutation of the HADHA gene, resulting in the skipping of exon 16 with an in-frame 69-bp deletion. Patient 3 was a compound heterozygosity of the HADHB gene, N307D/N389D. Patient 4, a 25-month-old baby, manifested recurrent episodes of lethargy, metabolic acidosis, elevated liver enzymes, and dark urine from the age of 10 months. Mutation analysis of the HADHB gene of patient 4 identified compound heterozygosity of N114D/N307D.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Erros Inatos do Metabolismo dos Aminoácidos
/
Complexos Multienzimáticos
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
/
Child, preschool
/
Female
/
Humans
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Male
/
Newborn
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2007
Tipo de documento:
Article