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Glutaric acidemia type I

Reviewed March 2007

What is glutaric acidemia type I?

Glutaric acidemia type I is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder 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.

How common is glutaric acidemia type I?

Glutaric acidemia type I occurs in approximately 1 of every 30,000 to 40,000 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.

What genes are related to glutaric acidemia type I?

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. This enzyme deficiency 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.

Related Gene(s)

Changes in this gene are associated with glutaric acidemia type I.

  • GCDH

How do people inherit 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.

Where can I find information about diagnosis or management of glutaric acidemia type I?

These resources address the diagnosis or management of glutaric acidemia type I and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/glutaric-acidemia-type-i)
  • Gene Review: Organic Acidemias Overview (http://www.ncbi.nlm.nih.gov/books/NBK1134)
  • Genetic Testing Registry: Glutaric aciduria, type 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268595)

You might also find information on the diagnosis or management of glutaric acidemia type I in Educational resources (http://www.ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/glutaric-acidemia-type-i/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about glutaric acidemia type I?

You may find the following resources about glutaric acidemia type I helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for glutaric acidemia type I?

  • GA I
  • Glutaric acidemia I
  • Glutaric acidemia type 1
  • Glutaric aciduria I
  • Glutaryl-CoA dehydrogenase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about glutaric acidemia type I?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding glutaric acidemia type I?

acids ; aciduria ; autosomal ; autosomal recessive ; breakdown ; cell ; CoA ; decreased muscle tone ; deficiency ; dehydrogenase ; disability ; enzyme ; fever ; gene ; infection ; inherited ; lysine ; macrocephaly ; muscle tone ; neurological ; newborn screening ; population ; progression ; protein ; recessive ; screening ; stress ; tryptophan

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Basinger AA, Booker JK, Frazier DM, Koeberl DD, Sullivan JA, Muenzer J. Glutaric acidemia type 1 in patients of Lumbee heritage from North Carolina. Mol Genet Metab. 2006 May;88(1):90-2. Epub 2006 Feb 8. (http://www.ncbi.nlm.nih.gov/pubmed/16466958?dopt=Abstract)
  • Funk CB, Prasad AN, Frosk P, Sauer S, Kölker S, Greenberg CR, Del Bigio MR. Neuropathological, biochemical and molecular findings in a glutaric acidemia type 1 cohort. Brain. 2005 Apr;128(Pt 4):711-22. Epub 2005 Feb 2. (http://www.ncbi.nlm.nih.gov/pubmed/15689364?dopt=Abstract)
  • Gene Review: Organic Acidemias Overview (http://www.ncbi.nlm.nih.gov/books/NBK1134)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15774829?dopt=Abstract)
  • OMIM: GLUTARIC ACIDEMIA I (http://omim.org/entry/231670)
  • Hedlund GL, Longo N, Pasquali M. Glutaric acidemia type 1. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):86-94. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16602100?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16641220?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15505397?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/14705106?dopt=Abstract)
  • Kölker S, Koeller DM, Sauer S, Hörster F, Schwab MA, Hoffmann GF, Ullrich K, Okun JG. Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004;27(6):805-12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15505385?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15985591?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15922108?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15505392?dopt=Abstract)
  • Screening, Technology and Research in Genetics (http://www.newbornscreening.info/Parents/organicaciddisorders/GA1.html)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/12888985?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15505388?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2007
Published: December 16, 2014