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Study of inborn errors of metabolism in urine from patients with unexplained mental retardation

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

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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Abbreviations

ADSL:

Adenylosuccinate lyase

AGAT:

Arginine-glycine amidinotransferase

CCDS:

Cerebral creatine deficiency syndromes

CDG:

Congenital disorders of glycosylation

Cr:

Creatine

Crn:

Creatinine

CRTR:

Creatine transporter deficiency

DPD:

Dihydropyrimidine dehydrogenase

GAA:

Guanidinoacetate

GAMT:

Guanidinoacetate methyltransferase

GC/MS:

Gas chromatography/mass spectrometry

¹H-MRS:

Proton magnetic resonance spectroscopy

HPLC:

High-pressure liquid chromatography

HPLC-MS/MS:

Electrospray ionization tandem mass spectrometry

IEM:

Inborn error of metabolism

MMACHC:

Methylmalonic aciduria CbLC complementation group

MMADHC:

Methylmalonic aciduria CbLD complementation group

MR:

Mental retardation

MRI:

Magnetic resonance imaging

OTC:

Ornithine transcarbamylase

PKU:

Phenylketonuria

S-Ado:

Succinyladenosine

SAICAr:

Succinylamino-imidazole carboxamide riboside

SUCLA-2:

Succinyl-coenzyme A (CoA) ligase

UMP:

Uridine monophosphate

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Acknowledgements

We thank the patients, their families, and the institutions for mentally handicapped persons for their collaboration. The study was financially supported by grants FIS 05/1200, FIS PI051180, CAIXA GIRONA, and the Alicia Koplowitz Foundation. The groups are funded by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII.

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Authors and Affiliations

  1. Pediatric Neurology, Hospital Sant Joan de Déu, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Esplugues, Spain

    Angela Sempere, Angels García-Cazorla & Jaume Campistol

  2. Division of Inborn Errors of Metabolism (IBC), Department of Biochemistry and Molecular Genetics, Hospital Clínic and CIBERER, ISCIII, Barcelona, Spain

    Angela Arias, Guillermo Farré, Judith García-Villoria & Antonia Ribes

  3. Centro de Diagnóstico de Enfermedades Moleculares, Departamento de Biología Molecular CBM-SO, Facultad de Ciencias, Universidad Autónoma and CIBERER, ISCIII, 28049, Madrid, Spain

    Pilar Rodríguez-Pombo, Lurdes R. Desviat & Begoña Merinero

  4. Departamento de Bioquímica Clínica, Hospital Sant Joan de Déu, Passeig Sant Joan de Dèu, 2, 08950, Esplugues, Barcelona, Spain

    Maria A. Vilaseca & Rafael Artuch

Authors
  1. Angela Sempere
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  2. Angela Arias
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  3. Guillermo Farré
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  4. Judith García-Villoria
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  5. Pilar Rodríguez-Pombo
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  6. Lurdes R. Desviat
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  7. Begoña Merinero
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  8. Angels García-Cazorla
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  9. Maria A. Vilaseca
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  10. Antonia Ribes
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  11. Rafael Artuch
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  12. Jaume Campistol
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Corresponding author

Correspondence to Rafael Artuch.

Additional information

Communicated by: Georg Hoffmann

References to electronic databases: OMIM 602360, OMIM 601240, OMIM 300352, OMIM 103050, OMIM 274270, OMIM 300322, OMIM 258900, OMIM 261000, OMIM 311250, OMIM 606054, OMIM 60983, OMIM 611935, OMIM 603921, OMIM 243500, OMIM 231670, OMIM 210200, OMIM 300256, http://www.hgvs.org.mutnomen.

Competing interest: None declared

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Sempere, A., Arias, A., Farré, G. et al. Study of inborn errors of metabolism in urine from patients with unexplained mental retardation. J Inherit Metab Dis 33, 1–7 (2010). https://doi.org/10.1007/s10545-009-9004-y

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  • DOI: https://doi.org/10.1007/s10545-009-9004-y

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