Complementary dietary treatment using lysine-free, arginine-fortified amino acid supplements in glutaric aciduria type I - A decade of experience

Stefan Kölker, S. P Nikolas Boy, Jana Heringer, Edith Müller, Esther M. Maier, Regina Ensenauer, Chris Mühlhausen, Andrea Schlune, Cheryl R. Greenberg, David Koeller, Georg F. Hoffmann, Gisela Haege, Peter Burgard

Research output: Contribution to journalArticle

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Abstract

The cerebral formation and entrapment of neurotoxic dicarboxylic metabolites (glutaryl-CoA, glutaric and 3-hydroxyglutaric acid) are considered to be important pathomechanisms of striatal injury in glutaric aciduria type I (GA-I). The quantitatively most important precursor of these metabolites is lysine. Recommended therapeutic interventions aim to reduce lysine oxidation (low lysine diet, emergency treatment to minimize catabolism) and to enhance physiologic detoxification of glutaryl-CoA via formation of glutarylcarnitine (carnitine supplementation). It has been recently shown in Gcdh-/- mice that cerebral lysine influx and oxidation can be modulated by arginine which competes with lysine for transport at the blood-brain barrier and the inner mitochondrial membrane [Sauer et al., Brain 134 (2011) 157-170]. Furthermore, short-term outcome of 12 children receiving arginine-fortified diet showed very promising results [Strauss et al., Mol. Genet. Metab. 104 (2011) 93-106]. Since lysine-free, arginine-fortified amino acid supplements (AAS) are commercially available and used in Germany for more than a decade, we evaluated the effect of arginine supplementation in a cohort of 34 neonatally diagnosed GA-I patients (median age, 7.43years; cumulative follow-up period, 221.6patientyears) who received metabolic treatment according to a published guideline [Kölker et al., J. Inherit. Metab. Dis. 30 (2007) 5-22]. Patients used one of two AAS product lines during the first year of life, resulting in differences in arginine consumption [group 1 (Milupa Metabolics): mean=111mg arginine/kg; group 2 (Nutricia): mean=145mg arginine/kg; p

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalMolecular Genetics and Metabolism
Volume107
Issue number1-2
DOIs
StatePublished - Sep 2012

Fingerprint

Lysine
Arginine
Amino Acids
Nutrition
Metabolites
Therapeutics
Diet
Viverridae
Corpus Striatum
Oxidation
Detoxification
Emergency Treatment
Carnitine
Mitochondrial Membranes
Glutaric Acidemia I
Blood-Brain Barrier
Germany
Brain
Guidelines
Membranes

Keywords

  • Arginine
  • Diet
  • Dystonia
  • Glutaric aciduria type I
  • Guideline
  • Lysine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Complementary dietary treatment using lysine-free, arginine-fortified amino acid supplements in glutaric aciduria type I - A decade of experience. / Kölker, Stefan; Boy, S. P Nikolas; Heringer, Jana; Müller, Edith; Maier, Esther M.; Ensenauer, Regina; Mühlhausen, Chris; Schlune, Andrea; Greenberg, Cheryl R.; Koeller, David; Hoffmann, Georg F.; Haege, Gisela; Burgard, Peter.

In: Molecular Genetics and Metabolism, Vol. 107, No. 1-2, 09.2012, p. 72-80.

Research output: Contribution to journalArticle

Kölker, S, Boy, SPN, Heringer, J, Müller, E, Maier, EM, Ensenauer, R, Mühlhausen, C, Schlune, A, Greenberg, CR, Koeller, D, Hoffmann, GF, Haege, G & Burgard, P 2012, 'Complementary dietary treatment using lysine-free, arginine-fortified amino acid supplements in glutaric aciduria type I - A decade of experience', Molecular Genetics and Metabolism, vol. 107, no. 1-2, pp. 72-80. https://doi.org/10.1016/j.ymgme.2012.03.021
Kölker, Stefan ; Boy, S. P Nikolas ; Heringer, Jana ; Müller, Edith ; Maier, Esther M. ; Ensenauer, Regina ; Mühlhausen, Chris ; Schlune, Andrea ; Greenberg, Cheryl R. ; Koeller, David ; Hoffmann, Georg F. ; Haege, Gisela ; Burgard, Peter. / Complementary dietary treatment using lysine-free, arginine-fortified amino acid supplements in glutaric aciduria type I - A decade of experience. In: Molecular Genetics and Metabolism. 2012 ; Vol. 107, No. 1-2. pp. 72-80.
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