Glutaric acidemia type I (also called glutaric aciduria type I) is an inherited disorder in which the body is unable to process certain proteins properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.
People with glutaric acidemia type I have inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxylysine, and tryptophan, which are building blocks of protein. Excessive levels of these amino acids and their intermediate breakdown products can accumulate and cause damage to the brain, particularly the basal ganglia, which are regions that help control movement. Intellectual disability may also occur.
The severity of glutaric acidemia type I varies widely; some individuals are only mildly affected, while others have severe problems. In most cases, signs and symptoms first occur in infancy or early childhood, but in a small number of affected individuals, the disorder first becomes apparent in adolescence or adulthood.
Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.
Glutaric acidemia type I occurs in approximately 1 in 100,000 individuals. It is much more common in the Amish community and in the Ojibwa population of Canada, where up to 1 in 300 newborns may be affected.
Mutations in the GCDH gene cause glutaric acidemia type I. The GCDH gene provides instructions for making the enzyme glutaryl-CoA dehydrogenase. This enzyme is involved in processing the amino acids lysine, hydroxylysine, and tryptophan.
Mutations in the GCDH gene prevent production of the enzyme or result in the production of a defective enzyme that cannot function. A shortage (deficiency) of this enzyme allows lysine, hydroxylysine and tryptophan and their intermediate breakdown products to build up to abnormal levels, especially at times when the body is under stress.
The intermediate breakdown products resulting from incomplete processing of lysine, hydroxylysine, and tryptophan can damage the brain, particularly the basal ganglia, causing the signs and symptoms of glutaric acidemia type I.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- GA I
- Glutaric acidemia I
- Glutaric acidemia type 1
- Glutaric aciduria I
- Glutaryl-CoA dehydrogenase deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
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- Gerstner B, Gratopp A, Marcinkowski M, Sifringer M, Obladen M, Bührer C. Glutaric acid and its metabolites cause apoptosis in immature oligodendrocytes: a novel mechanism of white matter degeneration in glutaryl-CoA dehydrogenase deficiency. Pediatr Res. 2005 Jun;57(6):771-6. Epub 2005 Mar 17. Citation on PubMed
- Guerreiro G, Faverzani J, Jacques CED, Marchetti DP, Sitta A, de Moura Coelho D, Kayser A, Kok F, Athayde L, Manfredini V, Wajner M, Vargas CR. Oxidative damage in glutaric aciduria type I patients and the protective effects of l-carnitine treatment. J Cell Biochem. 2018 Dec;119(12):10021-10032. doi: 10.1002/jcb.27332. Epub 2018 Aug 20. Citation on PubMed
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- Kölker S, Boy SP, Heringer J, Müller E, Maier EM, Ensenauer R, Mühlhausen C, Schlune A, Greenberg CR, Koeller DM, Hoffmann GF, Haege G, Burgard P. Complementary dietary treatment using lysine-free, arginine-fortified amino acid supplements in glutaric aciduria type I - A decade of experience. Mol Genet Metab. 2012 Sep;107(1-2):72-80. doi: 10.1016/j.ymgme.2012.03.021. Epub 2012 Apr 4. Citation on PubMed
- Kölker S, Garbade SF, Greenberg CR, Leonard JV, Saudubray JM, Ribes A, Kalkanoglu HS, Lund AM, Merinero B, Wajner M, Troncoso M, Williams M, Walter JH, Campistol J, Martí-Herrero M, Caswill M, Burlina AB, Lagler F, Maier EM, Schwahn B, Tokatli A, Dursun A, Coskun T, Chalmers RA, Koeller DM, Zschocke J, Christensen E, Burgard P, Hoffmann GF. Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency. Pediatr Res. 2006 Jun;59(6):840-7. Epub 2006 Apr 26. Citation on PubMed
- Kölker S, Greenberg CR, Lindner M, Müller E, Naughten ER, Hoffmann GF. Emergency treatment in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004;27(6):893-902. Review. Citation on PubMed
- Kölker S, Koeller DM, Okun JG, Hoffmann GF. Pathomechanisms of neurodegeneration in glutaryl-CoA dehydrogenase deficiency. Ann Neurol. 2004 Jan;55(1):7-12. Review. Citation on PubMed
- Külkens S, Harting I, Sauer S, Zschocke J, Hoffmann GF, Gruber S, Bodamer OA, Kölker S. Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency. Neurology. 2005 Jun 28;64(12):2142-4. Citation on PubMed
- Lehnert W, Sass JO. Glutaconyl-CoA is the main toxic agent in glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I). Med Hypotheses. 2005;65(2):330-3. Citation on PubMed
- Lindner M, Kölker S, Schulze A, Christensen E, Greenberg CR, Hoffmann GF. Neonatal screening for glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004;27(6):851-9. Review. Citation on PubMed
- Pokora P, Jezela-Stanek A, Różdżyńska-Świątkowska A, Jurkiewicz E, Bogdańska A, Szymańska E, Rokicki D, Ciara E, Rydzanicz M, Stawiński P, Płoski R, Tylki-Szymańska A. Mild phenotype of glutaric aciduria type 1 in polish patients - novel data from a group of 13 cases. Metab Brain Dis. 2019 Apr;34(2):641-649. doi: 10.1007/s11011-018-0357-5. Epub 2018 Dec 20. Citation on PubMed or Free article on PubMed Central
- Screening, Technology and Research in Genetics
- Shadmehri AA, Fattahi N, Pourreza MR, Koohiyan M, Zarifi S, Darbouy M, Sharifi R, Tavakkoly Bazzaz J, Tabatabaiefar MA. Molecular genetic study of glutaric aciduria, type I: Identification of a novel mutation. J Cell Biochem. 2019 Mar;120(3):3367-3372. doi: 10.1002/jcb.27607. Epub 2018 Sep 11. Citation on PubMed
- Strauss KA, Brumbaugh J, Duffy A, Wardley B, Robinson D, Hendrickson C, Tortorelli S, Moser AB, Puffenberger EG, Rider NL, Morton DH. Safety, efficacy and physiological actions of a lysine-free, arginine-rich formula to treat glutaryl-CoA dehydrogenase deficiency: focus on cerebral amino acid influx. Mol Genet Metab. 2011 Sep-Oct;104(1-2):93-106. doi: 10.1016/j.ymgme.2011.07.003. Epub 2011 Jul 12. Citation on PubMed
- Strauss KA, Puffenberger EG, Robinson DL, Morton DH. Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet C Semin Med Genet. 2003 Aug 15;121C(1):38-52. Citation on PubMed
- Wajner M, Kölker S, Souza DO, Hoffmann GF, de Mello CF. Modulation of glutamatergic and GABAergic neurotransmission in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004;27(6):825-8. Review. Citation on PubMed