A Korean Female Patient with Thiamine-responsive Pyruvate Dehydrogenase Complex Deficiency Due to a Novel Point Mutation (Y161C)in the PDHA1 Gene
Journal of Korean Medical Science
;
: 800-804, 2006.
Artigo
em Inglês
| WPRIM
| ID: wpr-14646
ABSTRACT
Pyruvate dehydrogenase complex (PDHC) deficiency is mostly due to mutations in the X-linked E1alpha subunit gene (PDHA1). Some of the patients with PDHC deficiency showed clinical improvements with thiamine treatment. We report the results of biochemical and molecular analysis in a female patient with lactic acidemia. The PDHC activity was assayed at different concentrations of thiamine pyrophosphate (TPP). The PDHC activity showed null activity at low TPP concentration (1 x 10(-3) mM), but significantly increased at a high TPP concentration (1 mM). Sequencing analysis of PDHA1 gene of the patient revealed a substitution of cysteine for tyrosine at position 161 (Y161C). Thiamine treatment resulted in reduction of the patient's serum lactate concentration and dramatic clinical improvement. Biochemical, molecular, and clinical data suggest that this patient has a thiamine-responsive PDHC deficiency due to a novel mutation, Y161C. Therefore, to detect the thiamine responsiveness it is necessary to measure activities of PDHC not only at high but also at low concentration of TPP.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Tiamina
/
Tiamina Pirofosfato
/
Doença da Deficiência do Complexo de Piruvato Desidrogenase
/
Células Cultivadas
/
Mutação Puntual
/
Piruvato Desidrogenase (Lipoamida)
Limite:
Feminino
/
Humanos
/
Recém-Nascido
Idioma:
Inglês
Revista:
Journal of Korean Medical Science
Ano de publicação:
2006
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS