A three-tier algorithm for guanidinoacetate methyltransferase (GAMT) deficiency newborn screening.
Mol Genet Metab
; 118(3): 173-177, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-27233226
ABSTRACT
BACKGROUND:
Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine biosynthesis presenting with epilepsy and developmental delay in infancy. Excellent developmental outcomes have been reported for infants treated from birth due to a family history. The BC Newborn Screening Program initiated a 3year pilot screening study for GAMT deficiency to evaluate the performance of a novel three-tiered screening approach.METHODS:
Over 36months all bloodspots submitted for routine newborn screening were included in the pilot study (de-identified). Initial GAA measurement was integrated into the standard acylcarnitine/amino acid first-tier assay. All samples with elevated GAA were subjected to second-tier GAA analysis by LC-MS/MS integrated into an existing branched-chain amino acid (MSUD) method. GAMT gene sequencing was completed on the original bloodspot for all specimens with elevated GAA on the second-tier test. The protocol allowed for re-identification for treatment of any specimen with one or two likely pathogenic GAMT mutations.RESULTS:
Over the study period 135,372 specimens were tested with 259 (0.19%) over the first-tier GAA cut-off. The second-tier assay removed an interference falsely elevating GAA levels, and only 3 samples required genotyping. No mutations were identified in any samples, all were deemed negative screens and no follow-up was initiated.CONCLUSIONS:
A three-tier algorithm for GAMT newborn screening showed excellent test performance with zero false positives. No cases were detected, supporting a low incidence for this disorder. Given the low incremental costs and evidence of positive outcomes with early intervention, GAMT deficiency remains an excellent candidate for newborn screening.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Triagem Neonatal
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Guanidinoacetato N-Metiltransferase
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Transtornos do Desenvolvimento da Linguagem
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Transtornos dos Movimentos
Tipo de estudo:
Diagnostic_studies
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Guideline
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Prognostic_studies
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Screening_studies
Limite:
Humans
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Newborn
Idioma:
En
Revista:
Mol Genet Metab
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2016
Tipo de documento:
Article