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Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation

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Abstract

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the biosynthesis of creatine (Cr). So far, reports have not focused on the description of developmental abilities in this disorder. Here, we present the result of formal testing of developmental abilities in a GAMT-deficient patient. Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a severe language production delay and nearly normal nonverbal development. Treatment with oral Cr supplementation led to partial restoration of the cerebral Cr concentration and a clinically remarkable acceleration of language production development. In contrast to clinical observation, formal testing showed a rather harmonic developmental delay before therapy and a general improvement, but no specific acceleration of language development after therapy. From our case, we conclude that in GAMT deficiency language delay is not always more prominent than delays in other developmental areas. The discrepancy between the clinical impression and formal testing underscores the importance of applying standardized tests in children with developmental delays. Screening for Cr deficiency by metabolite analysis of body fluids or proton magnetic resonance spectroscopy of the brain deficiency should be considered in any child with global developmental delay/mental retardation lacking clues for an alternative etiology.

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Abbreviations

AGAT:

L-arginine-glycine amidinotransferase (OMIM 601360)

CRTR:

Creatine transporter (OMIM 30036)

GAA:

Guanidinoacetic acid

1HMRS:

Proton magnetic resonance spectroscopy

Cr:

Creatine

GAMT:

Guanidinoacetate N-methyltransferase (OMIM 601240)

GAMTD:

Guanidinoacetate N-methyltransferase deficiency

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Authors and Affiliations

  1. University Medical Center Groningen, Beatrix Children’s Hospital, University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands

    Krijn T. Verbruggen & Francjan J. van Spronsen

  2. Department of University Medical Center Groningen, Otorhinolaryngology, University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands

    Wilma A. Knijff & Siena M. Goorhuis-Brouwer

  3. Department of University Medical Center Groningen, Pediatric Neurology, University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands

    Roelineke J. Soorani-Lunsing

  4. University Medical Center Groningen, Department of Radiology, P.O. Box 30001, 9700 RB, Groningen, The Netherlands

    Paul E. Sijens

  5. Metabolic Unit, Department of Clinical Chemistry, VU University Medical Centre, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands

    Nanda M. Verhoeven & Gajja S. Salomons

Authors
  1. Krijn T. Verbruggen
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  2. Wilma A. Knijff
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  3. Roelineke J. Soorani-Lunsing
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  4. Paul E. Sijens
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  5. Nanda M. Verhoeven
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  6. Gajja S. Salomons
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  7. Siena M. Goorhuis-Brouwer
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  8. Francjan J. van Spronsen
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Correspondence to Krijn T. Verbruggen.

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Verbruggen, K.T., Knijff, W.A., Soorani-Lunsing, R.J. et al. Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation. Eur J Pediatr 166, 921–925 (2007). https://doi.org/10.1007/s00431-006-0340-8

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  • DOI: https://doi.org/10.1007/s00431-006-0340-8

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