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Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision
Author(s) -
Boy Nikolas,
Mühlhausen Chris,
Maier Esther M.,
Heringer Jana,
Assmann Birgit,
Burgard Peter,
Dixon Marjorie,
Fleissner Sandra,
Greenberg Cheryl R.,
Harting Inga,
Hoffmann Georg F.,
Karall Daniela,
Koeller David M.,
Krawinkel Michael B.,
Okun Jürgen G.,
Opladen Thomas,
Posset Roland,
Sahm Katja,
Zschocke Johannes,
Kölker Stefan
Publication year - 2017
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-016-9999-9
Subject(s) - glutaric acid , carnitine , newborn screening , medicine , pediatrics , endocrinology , biology , biochemistry
Abstract Glutaric aciduria type I (GA‐I; synonym, glutaric acidemia type I) is a rare inherited metabolic disease caused by deficiency of glutaryl‐CoA dehydrogenase located in the catabolic pathways of L‐lysine, L‐hydroxylysine, and L‐tryptophan. The enzymatic defect results in elevated concentrations of glutaric acid, 3‐hydroxyglutaric acid, glutaconic acid, and glutaryl carnitine in body tissues, which can be reliably detected by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Most untreated individuals with GA‐I experience acute encephalopathic crises during the first 6 years of life that are triggered by infectious diseases, febrile reaction to vaccinations, and surgery. These crises result in striatal injury and consequent dystonic movement disorder; thus, significant mortality and morbidity results. In some patients, neurologic disease may also develop without clinically apparent crises at any age. Neonatal screening for GA‐I us being used in a growing number of countries worldwide and is cost effective. Metabolic treatment, consisting of low lysine diet, carnitine supplementation, and intensified emergency treatment during catabolism, is effective treatment and improves neurologic outcome in those individuals diagnosed early; treatment after symptom onset, however, is less effective. Dietary treatment is relaxed after age 6 years and should be supervised by specialized metabolic centers. The major aim of this second revision of proposed recommendations is to re‐evaluate the previous recommendations (Kölker et al. J Inherit Metab Dis 30:5‐22, 2007b; J Inherit Metab Dis 34:677‐694, 2011) and add new research findings, relevant clinical aspects, and the perspective of affected individuals.