Guanidinoacetate methyltransferase deficiency: First steps to newborn screening for a treatable neurometabolic disease
| Autor: | O.T. Betsalel, Saadet Mercimek-Mahmutoglu, Graham Sinclair, Gajja S. Salomons, J. Nelson, Lawrence Sweetman, Warsha A. Kanhai, P. Ashcraft, S.J.M. van Dooren, C.A.J.M. Jakobs, O.J. Michel |
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| Přispěvatelé: | Clinical chemistry, Human genetics, NCA - Childhood White Matter Diseases, Neuroscience Campus Amsterdam - Childhood White Matter Diseases |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Heterozygote medicine.medical_specialty Pediatrics Endocrinology Diabetes and Metabolism DNA Mutational Analysis Molecular Sequence Data Population Guanidinoacetate methyltransferase deficiency Biochemistry Neurometabolic disease Neonatal Screening Endocrinology Gene Frequency SDG 3 - Good Health and Well-being Genetics medicine Humans Language Development Disorders Global developmental delay education Molecular Biology Alleles Sequence Deletion Carrier signal education.field_of_study Newborn screening Movement Disorders Base Sequence Chemistry Infant Newborn Creatine medicine.disease Surgery Guanidinoacetate N-methyltransferase Mutagenesis Insertional Early Diagnosis Cohort Female Guanidinoacetate N-Methyltransferase |
| Zdroj: | Mercimek-Mahmutoglu, S, Sinclair, G, van Dooren, S J M, Kanhai, W, Ashcraft, P, Michel, O J, Nelson, J, Betsalel, O T, Sweetman, L, Jakobs, C A J M & Salomons, G S 2012, ' Guanidinoacetate methyltransferase deficiency: First steps to newborn screening for a treatable neurometabolic disease ', Molecular Genetics and Metabolism, vol. 107, no. 3, pp. 433-437 . https://doi.org/10.1016/j.ymgme.2012.07.022 Molecular Genetics and Metabolism, 107(3), 433-437. Academic Press Inc. |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2012.07.022 |
| Popis: | Background: GAMT deficiency is an autosomal recessive disorder of creatine biosynthesis resulting in severe neurological complications in untreated patients. Currently available treatment is only successful to stop disease progression, but is not sufficient to reverse neurological complications occurring prior to diagnosis. Normal neurodevelopmental outcome in a patient, treated in the newborn period, highlights the importance of early diagnosis. Methods: Targeted mutation analysis (c.59G>C and c.327G>A) in the GAMT gene by the QIAxcel system and GAA measurement by a novel two-tier method were performed in 3000 anonymized newborn blood dot spot cards. Results: None of the targeted mutations were detected in any newborn. Two novel heterozygous variants (c.283_285dupGTC; p.Val95dup and c.278_283delinsCTCGATGCAC; p.Asp93AlafsX35) were identified by coincidence. Carrier frequency for these insertion/deletion types of GAMT mutations was 1/1475 in this small cohort of newborns. GAA levels were at or above the 99th percentile (3.12μmol/l) in 4 newborns. Second-tier testing showed normal results for 4 newborns revealing 0.1% false positive rate. No GAMT mutations were identified in 4 of the newborns with elevated GAA levels in the first tier testing. Conclusion: This is the first two-tier study to investigate carrier frequency of GAMT deficiency in the small cohort of newborn population to establish evidence base for the first steps toward newborn screening for this treatable neurometabolic disorder. © 2012 Elsevier Inc. |
| Databáze: | OpenAIRE |
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