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Low lysine diet in glutaric aciduria type I – effect on anthropometric and biochemical follow-up parameters

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Background

Metabolic treatment in glutaric aciduria type I (GA-I) including a low lysine diet with lysine-free, tryptophan-reduced amino acid supplements (AAS), carnitine supplementation and early start of emergency treatment during putatively threatening episodes of intermittent febrile illness dramatically improves the outcome and thus has been recommended by an international guideline group (Kölker et al, J Inherit Metab Dis 30:5–22, 2007). However, possible affection of linear growth, weight gain and biochemical follow-up monitoring has not been studied systematically.

Methods

Thirty-three patients (n = 29 asymptomatic, n = 4 dystonic) with GA-I who have been identified by newborn screening in Germany from 1999 to 2009 were followed prospectively during the first six years of life. Dietary treatment protocols, anthropometrical and biochemical parameters were longitudinally evaluated.

Results

Mean daily intake as percentage of guideline recommendations was excellent for lysine (asymptomatic patients: 101 %; dystonic patients: 103 %), lysine-free, tryptophan-reduced AAS (108 %; 104 %), energy (106 %; 110 %), and carnitine (92 %; 102 %). Low lysine diet did not affect weight gain (mean SDS 0.05) but mildly impaired linear growth in asymptomatic patients (mean SDS −0.38), while dystonic patients showed significantly reduced weight gain (mean SDS −1.32) and a tendency towards linear growth retardation (mean SDS −1.03). Patients treated in accordance with recent recommendations did not show relevant abnormalities of routine biochemical follow-up parameters.

Interpretation

Low lysine diet promotes sufficient intake of essential nutrients and anthropometric development in asymptomatic children up to age 6 year, whereas individualized nutritional concepts are required for dystonic patients. Revised recommendations for biochemical monitoring might be required for asymptomatic patients.

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Abbreviations

3-OH-GA:

3-hydroxyglutaric acid

AAS:

Amino acid supplements (lysine-free tryptophan-reduced, fortified with minerals, trace elements, and vitamins)

ALAT:

Alanine aminotransferase

ANOVA:

Analysis of variance

ASAT:

Aspartate aminotransferase

C5DC:

Glutarylcarnitine

FAD:

Flavin adenine dinucleotide

GA:

Glutaric acid

GA-I:

Glutaric aciduria type I

GCDH:

Glutaryl-CoA dehydrogenase

GC/MS:

Gas chromatography/mass spectrometry

MCV:

Mean corpuscular volume

NBS:

Newborn screening

SD(S):

Standard deviation (score)

TCA:

Tricarboxylic acid cycle

TSCSREG:

Times series cross sectional regression analysis

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Acknowledgements & Funding

The study was supported by grants from the Kindness for Kids Foundation, Munich, Germany, and was continued with funding from the European Union for the project E-IMD (EAHC no. 2010 12 01), in the framework of the Health Programme 2008–2013 – both to S. K. and G. F. H. The authors declare no conflict of interest. We thank the patients with GA-I and their parents for participation in this study.

The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Hospital Heidelberg, Heidelberg, Germany

    Nikolas Boy, Gisela Haege, Jana Heringer, Georg F. Hoffmann, Edith Müller, Peter Burgard & Stefan Kölker

  2. Department of General Pediatrics, Division of Neuropediatrics, University Hospital Heidelberg, Heidelberg, Germany

    Birgit Assmann

  3. Department of General Pediatrics, Children’s Hospital, Heinrich-Heine-Universität Düsseldorf, Dusseldorf, Germany

    Birgit Assmann

  4. Department of Pediatrics, University Medical Center, Hamburg, Hamburg, Germany

    Chris Mühlhausen

  5. Research Center, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

    Regina Ensenauer & Esther M. Maier

  6. Department of Neuropediatrics, University Children’s Hospital, Ruhr-University Bochum, Bochum, Germany

    Thomas Lücke

  7. Division of Inherited Metabolic Diseases, Centre for Child and Adolescent Medicine, Clinic I, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Stefan Kölker

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  1. Nikolas Boy
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  2. Gisela Haege
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  9. Georg F. Hoffmann
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  11. Peter Burgard
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  12. Stefan Kölker
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Corresponding author

Correspondence to Stefan Kölker.

Additional information

Communicated by: Johan Lodewijk Karel Van Hove

Peter Burgard and Stefan Kölker contributed equally

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Boy, N., Haege, G., Heringer, J. et al. Low lysine diet in glutaric aciduria type I – effect on anthropometric and biochemical follow-up parameters. J Inherit Metab Dis 36, 525–533 (2013). https://doi.org/10.1007/s10545-012-9517-7

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  • DOI: https://doi.org/10.1007/s10545-012-9517-7

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