TY - JOUR
T1 - Recommendations for diagnosing and managing individuals with glutaric aciduria type 1
T2 - third revision
AU - Boy, Nikolas
AU - Mühlhausen, Chris
AU - Maier, Esther M.
AU - Ballhausen, Diana
AU - Baumgartner, Matthias R.
AU - Beblo, Skadi
AU - Burgard, Peter
AU - Chapman, Kimberly A.
AU - Dobbelaere, Dries
AU - Heringer-Seifert, Jana
AU - Fleissner, Sandra
AU - Grohmann-Held, Karina
AU - Hahn, Gabriele
AU - Harting, Inga
AU - Hoffmann, Georg F.
AU - Jochum, Frank
AU - Karall, Daniela
AU - Konstantopoulous, Vassiliki
AU - Krawinkel, Michael B.
AU - Lindner, Martin
AU - Märtner, E. M.Charlotte
AU - Nuoffer, Jean Marc
AU - Okun, Jürgen G.
AU - Plecko, Barbara
AU - Posset, Roland
AU - Sahm, Katja
AU - Scholl-Bürgi, Sabine
AU - Thimm, Eva
AU - Walter, Magdalena
AU - Williams, Monique
AU - Dahl, Stephan vom
AU - Ziagaki, Athanasia
AU - Zschocke, Johannes
AU - Kölker, Stefan
N1 - FUNDING INFORMATION:
The development process for the third guideline revision
was financially supported by the German Society of Paediatrics (Deutsche Gesellschaft für Kinder- und Jugendmedizin, DGKJ), logistically supported by the German
Association for Paediatric Metabolic Disorders (Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen, APS)
and methodically supported by the National Association
of Scientific Medical Societies (Arbeitsgemeinschaft Wissenschaftlich-Medizinische Fachgesellschaften, AWMF).
The guideline process has not been influenced by the
financing organisations.
Publisher Copyright:
This article is protected by copyright. All rights reserved.
PY - 2022/10/11
Y1 - 2022/10/11
N2 - Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age three (to six) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, i.e. age 6 years. However, impact of dietary relaxation on long-term outcome is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations 1-3 and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes. This article is protected by copyright. All rights reserved.
AB - Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age three (to six) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, i.e. age 6 years. However, impact of dietary relaxation on long-term outcome is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations 1-3 and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes. This article is protected by copyright. All rights reserved.
UR - http://www.scopus.com/inward/record.url?scp=85142196706&partnerID=8YFLogxK
U2 - 10.1002/jimd.12566
DO - 10.1002/jimd.12566
M3 - Article
C2 - 36221165
AN - SCOPUS:85142196706
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
ER -