Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.
Mol Genet Metab
; 109(3): 260-8, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23660394
ABSTRACT
Cerebral creatine deficiency syndromes (CCDS) are a group of inborn errors of creatine metabolism that involve AGAT and GAMT for creatine biosynthesis disorders and SLC6A8 for creatine transporter (CT1) deficiency. Deficiencies in the three enzymes can be distinguished by intermediate metabolite levels, and a definitive diagnosis relies on the presence of deleterious mutations in the causative genes. Mutations and unclassified variants were identified in 41 unrelated patients, and 22 of these mutations were novel. Correlation of sequencing and biochemical data reveals that using plasma guanidinoacetate (GAA) as a biomarker has 100% specificity for both AGAT and GAMT deficiencies, but AGAT deficiency has decreased sensitivity in this assay. Furthermore, the urine creatinecreatinine ratio is an effective screening test with 100% specificity in males suspected of having creatine transporter deficiency. This test has a high false-positive rate due to dietary factors or dilute urine samples and lacks sensitivity in females. We conclude that biochemical screening for plasma GAA and measuring of the urine creatinecreatinine ratio should be performed for suspected CCDS patients prior to sequencing. Also, based on the results of this study, we feel that sequencing should only be considered if a patient has abnormal biochemical results on repeat testing.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Distúrbios da Fala
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Creatina
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Encefalopatias Metabólicas Congênitas
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Deficiência Intelectual Ligada ao Cromossomo X
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Guanidinoacetato N-Metiltransferase
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Proteínas da Membrana Plasmática de Transporte de Neurotransmissores
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Amidinotransferases
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Erros Inatos do Metabolismo dos Aminoácidos
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Transtornos do Desenvolvimento da Linguagem
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Deficiência Intelectual
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
Mol Genet Metab
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos