Clinical and metabolic findings in patients with methionine adenosyltransferase I/III deficiency detected by newborn screening.
Mol Genet Metab
; 110(3): 218-21, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23993429
ABSTRACT
Persistent hypermethioninemia due to mutations in the MAT1A gene is often found during newborn screening (NBS) for homocystinuria due to cystathionine beta-synthase deficiency, however, outcomes and optimal management for these patients are not well established. We carried out a multicenter study of MAT I/III-deficient patients detected by NBS in four of the Spanish regional NBS programs. Data evaluated during NBS and follow-up for 18 patients included methionine and total homocysteine levels, clinical presentation parameters, genotypes, and development quotients. The birth prevalence was 1122,874. At detection 16 of the 18 patients exhibited elevations of plasma methionine above 60 µmol/L (mean 99.9 ± 38 µmol/L) and the mean value in confirmation tests was 301 µmol/L (91-899) µmol/L. All patients were asymptomatic. In four patients with more markedly elevated plasma methionines (>450 µmol/L) total homocysteine values were slightly elevated (about 20 µmol/L). The average follow-up period was 3 years 7 months (range 2-123 months). Most patients (83%) were heterozygous for the autosomal dominant Arg264His mutation and, with one exception, presented relatively low circulating methionine concentrations (<400 µM). Additional mutations identified in patients with mean confirmatory plasma methionines above 400 µM were Arg199Cys, Leu355Arg, and a novel mutation, Thr288Ala. During continued follow-up, the patients have been asymptomatic, and, to date, no therapeutic interventions have been utilized. Therefore, the currently available evidence shows that hypermethioninemia due to heterozygous MAT1A mutations such as Arg264His is a mild condition for which no treatment is necessary.
Palavras-chave
AdoMet/SAM; DQs; Developmental quotients; Homocysteine; MAT; MSCA; McCarthy Scales of Children's Abilities; Methionine adenosyltransferase; NBS; Newborn screening; Persistent hypermethioninemia; S-adenosylmethionine; WISC; Wechsler intelligence scale for children; newborn screening; tHcy; total homocysteine
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Erros Inatos do Metabolismo dos Aminoácidos
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Metionina Adenosiltransferase
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Female
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Humans
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Male
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Newborn
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article