Study of Inborn Errors of Metabolism in Urine from Patients with Unexplained Mental Retardation

Overview

Journal J Inherit Metab Dis

Publisher Wiley

Date 2010 Jan 6

PMID 20049533

Citations 12

Authors

Angela Sempere

Angela Arias

Guillermo Farre

Judith Garcia-Villoria

Pilar Rodriguez-Pombo

Lurdes R Desviat

Begona Merinero

Angels Garcia-Cazorla

Maria A Vilaseca

Antonia Ribes

Rafael Artuch

Jaume Campistol

Affiliations

Soon will be listed here.

Abstract

Mental retardation (MR) is a common disorder frequently of unknown origin. Because there are few studies regarding MR and inborn errors of metabolism (IEM), we aimed to identify patients with IEM from a cohort of 944 patients with unexplained MR. Biochemical examinations such as determination of creatine (Cr) metabolites, acylcarnitines, purine, and pyrimidines in urine were applied. We found seven patients with IEM [three with cerebral Cr deficiency syndromes (CCDS)], one with adenylosuccinate lyase (ADSL) deficiency, and three, born before the neonatal metabolic screening program in Catalonia, with phenylketonuria (PKU). All told, they represent 0.8% of the whole cohort. All of them had additional symptoms such as epilepsy, movement disorders, autism, and other psychiatric disturbances. In conclusion, in patients with MR, it is essential to perform a thorough appraisal of the associated signs and symptoms, and in most disorders, it is necessary to apply specific analyses. In some cases, it is important to achieve an early diagnosis and therapy, which may reduce the morbimortality, and to offer genetic counselling.

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References

Matilainen R, Airaksinen E, Mononen T, LAUNIALA K, KAARIAINEN R . A population-based study on the causes of mild and severe mental retardation. Acta Paediatr. 1995; 84(3):261-6. DOI: 10.1111/j.1651-2227.1995.tb13626.x. View

Battaglia A, Carey J . Diagnostic evaluation of developmental delay/mental retardation: An overview. Am J Med Genet C Semin Med Genet. 2003; 117C(1):3-14. DOI: 10.1002/ajmg.c.10015. View

Ryan R, Sunada K . Medical evaluation of persons with mental retardation referred for psychiatric assessment. Gen Hosp Psychiatry. 1997; 19(4):274-80. DOI: 10.1016/s0163-8343(97)00023-6. View

Clark A, Rosenberg E, Almeida L, Wood T, Jakobs C, Stevenson R . X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology. Hum Genet. 2006; 119(6):604-10. DOI: 10.1007/s00439-006-0162-9. View

Hunter A . Outcome of the routine assessment of patients with mental retardation in a genetics clinic. Am J Med Genet. 1999; 90(1):60-8. DOI: 10.1002/(sici)1096-8628(20000103)90:1<60::aid-ajmg11>3.0.co;2-p. View

Espinos C, Pineda M, Martinez-Rubio D, Lupo V, Ormazabal A, Vilaseca M . Mutations in the urocanase gene UROC1 are associated with urocanic aciduria. J Med Genet. 2009; 46(6):407-11. DOI: 10.1136/jmg.2008.060632. View

Arias A, Corbella M, Fons C, Sempere A, Garcia-Villoria J, Ormazabal A . Creatine transporter deficiency: prevalence among patients with mental retardation and pitfalls in metabolite screening. Clin Biochem. 2007; 40(16-17):1328-31. DOI: 10.1016/j.clinbiochem.2007.07.010. View

Sempere A, Fons C, Arias A, Rodriguez-Pombo P, Colomer R, Merinero B . Creatine transporter deficiency in two adult patients with static encephalopathy. J Inherit Metab Dis. 2009; 32 Suppl 1:S91-6. DOI: 10.1007/s10545-009-1083-2. View

Arias A, Ormazabal A, Moreno J, Gonzalez B, Vilaseca M, Garcia-Villoria J . Methods for the diagnosis of creatine deficiency syndromes: a comparative study. J Neurosci Methods. 2006; 156(1-2):305-9. DOI: 10.1016/j.jneumeth.2006.03.005. View

10.

Zhang C, Xu K, Dave U, Wang Y, Matsumoto I . Inborn errors of metabolism discovered in Asian department of pediatrics and mental retardation research center. J Chromatogr B Biomed Sci Appl. 2000; 746(1):41-9. DOI: 10.1016/s0378-4347(00)00087-6. View

11.

Stockler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K . Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet. 1996; 58(5):914-22. PMC: 1914613. View

12.

van Karnebeek C, Jansweijer M, Leenders A, Offringa M, Hennekam R . Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness. Eur J Hum Genet. 2004; 13(1):6-25. DOI: 10.1038/sj.ejhg.5201279. View

13.

Tanaka K, Hine D, Lynn T, Lowe T . Gas-chromatographic method of analysis for urinary organic acids. II. Description of the procedure, and its application to diagnosis of patients with organic acidurias. Clin Chem. 1980; 26(13):1847-53. View

14.

Mercimek-Mahmutoglu S, Stoeckler-Ipsiroglu S, Adami A, Appleton R, Araujo H, Duran M . GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology. 2006; 67(3):480-4. DOI: 10.1212/01.wnl.0000234852.43688.bf. View

15.

Artuch R, Colome C, Sierra C, Brandi N, Lambruschini N, Campistol J . A longitudinal study of antioxidant status in phenylketonuric patients. Clin Biochem. 2004; 37(3):198-203. DOI: 10.1016/j.clinbiochem.2003.10.017. View

16.

Salerno C, DEufemia P, Finocchiaro R, Celli M, Spalice A, Iannetti P . Effect of D-ribose on purine synthesis and neurological symptoms in a patient with adenylosuccinase deficiency. Biochim Biophys Acta. 1999; 1453(1):135-40. DOI: 10.1016/s0925-4439(98)00093-3. View

17.

Stockler S, Schutz P, Salomons G . Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. Subcell Biochem. 2008; 46:149-66. DOI: 10.1007/978-1-4020-6486-9_8. View

18.

Newmeyer A, Cecil K, Schapiro M, Clark J, DeGrauw T . Incidence of brain creatine transporter deficiency in males with developmental delay referred for brain magnetic resonance imaging. J Dev Behav Pediatr. 2005; 26(4):276-82. DOI: 10.1097/00004703-200508000-00003. View

19.

van Karnebeek C, Scheper F, Abeling N, Alders M, Barth P, Hoovers J . Etiology of mental retardation in children referred to a tertiary care center: a prospective study. Am J Ment Retard. 2005; 110(4):253-67. DOI: 10.1352/0895-8017(2005)110[253:EOMRIC]2.0.CO;2. View

20.

Jurecka A, Tylki-Szymanska A, Zikanova M, Krijt J, Kmoch S . D-ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect. J Inherit Metab Dis. 2008; 31 Suppl 2:S329-32. DOI: 10.1007/s10545-008-0904-z. View