Clinical and molecular heterogeneity in patients with the cblD inborn error of cobalamin metabolism.
J Pediatr
; 154(4): 551-6, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19058814
ABSTRACT
OBJECTIVES:
To describe 3 patients with the cblD disorder, a rare inborn error of cobalamin metabolism caused by mutations in the MMADHC gene that can result in isolated homocystinuria, isolated methylmalonic aciduria, or combined homocystinuria and methylmalonic aciduria. STUDYDESIGN:
Patient clinical records were reviewed. Biochemical and somatic cell genetic studies were performed on cultured fibroblasts. Sequence analysis of the MMADHC gene was performed on patient DNA.RESULTS:
Patient 1 presented with isolated methylmalonic aciduria, patient 3 with isolated homocystinuria, and patient 2 with combined methylmalonic aciduria and homocystinuria. Studies of cultured fibroblasts confirmed decreased synthesis of adenosylcobalamin in patient 1, decreased synthesis of methylcobalamin in patient 3, and decreased synthesis of both cobalamin derivatives in patient 2. The diagnosis of cblD was established in each patient by complementation analysis. Mutations in the MMADHC gene were identified in all patients.CONCLUSIONS:
The results emphasize the heterogeneous clinical, cellular and molecular phenotype of the cblD disorder. The results of molecular analysis of the MMADHC gene are consistent with the hypothesis that mutations affecting the N terminus of the MMADHC protein are associated with methylmalonic aciduria, and mutations affecting the C terminus are associated with homocystinuria.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiência de Vitamina B 12
/
Cobamidas
/
Erros Inatos do Metabolismo dos Aminoácidos
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
J Pediatr
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Canadá