Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.
Mol Genet Metab
; 109(3): 260-8, 2013 Jul.
Article
en 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
Bases de datos:
MEDLINE
Asunto principal:
Trastornos del Habla
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Creatina
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Encefalopatías Metabólicas Innatas
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Discapacidad Intelectual Ligada al Cromosoma X
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Guanidinoacetato N-Metiltransferasa
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Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática
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Amidinotransferasas
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Errores Innatos del Metabolismo de los Aminoácidos
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Trastornos del Desarrollo del Lenguaje
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Discapacidad Intelectual
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Idioma:
En
Revista:
Mol Genet Metab
Asunto de la revista:
BIOLOGIA MOLECULAR
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BIOQUIMICA
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METABOLISMO
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos