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URL of this page: https://medlineplus.gov/genetics/gene/gldc/

GLDC gene

glycine decarboxylase

Normal Function

The GLDC gene provides instructions for making an enzyme called glycine dehydrogenase. This protein is one of four enzymes that work together in a group called the glycine cleavage system. Within cells, this system is active in specialized energy-producing centers called mitochondria.

As its name suggests, the glycine cleavage system breaks down a molecule called glycine by cutting (cleaving) it into smaller pieces. Glycine is an amino acid, which is a building block of proteins. This molecule also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. The breakdown of excess glycine when it is no longer needed is necessary for the normal development and function of nerve cells in the brain.

The breakdown of glycine by the glycine cleavage system produces a molecule called a methyl group. This molecule is added to and used by a vitamin called folate. Folate is required for many functions in the cell and is important for brain development.

Health Conditions Related to Genetic Changes

Nonketotic hyperglycinemia

Mutations in the GLDC gene account for about 80 percent of all cases of nonketotic hyperglycinemia. This condition is characterized by abnormally high levels of glycine in the body (hyperglycinemia). Affected individuals have serious neurological problems. The signs and symptoms of the condition vary in severity and can include severe breathing difficulties shortly after birth as well as weak muscle tone (hypotonia), seizures, and delayed development of milestones. More than 400 mutations have been identified in affected individuals. Many of these genetic changes alter single amino acids in glycine dehydrogenase. Other mutations insert or delete genetic material in the GLDC gene, or disrupt how genetic information from the gene is spliced together to make a blueprint for producing glycine dehydrogenase.

Some GLDC gene mutations lead to the production of a nonfunctional version of glycine dehydrogenase, while other mutations reduce but do not eliminate the enzyme's activity. When an altered version of this enzyme is incorporated into the glycine cleavage system, it impairs the system's ability to break down glycine. As a result, excess glycine can build up in the body's organs and tissues. In addition, the production of methyl groups for use by folate is reduced. It is unclear how these abnormalities contribute to the developmental disability, seizures, breathing difficulties, and other features characteristic of nonketotic hyperglycinemia.

More About This Health Condition

Other Names for This Gene

  • GCE
  • GCSP
  • GCSP_HUMAN
  • glycine cleavage system protein P
  • glycine decarboxylase P-protein
  • glycine dehydrogenase (decarboxylating)
  • glycine dehydrogenase (decarboxylating; glycine decarboxylase, glycine cleavage system protein P)
  • NKH

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Applegarth DA, Toone JR. Glycine encephalopathy (nonketotic hyperglycinemia): comments and speculations. Am J Med Genet A. 2006 Jan 15;140(2):186-8. doi: 10.1002/ajmg.a.31030. No abstract available. Citation on PubMed
  • Conter C, Rolland MO, Cheillan D, Bonnet V, Maire I, Froissart R. Genetic heterogeneity of the GLDC gene in 28 unrelated patients with glycine encephalopathy. J Inherit Metab Dis. 2006 Feb;29(1):135-42. doi: 10.1007/s10545-006-0202-6. Citation on PubMed
  • Coughlin CR 2nd, Swanson MA, Kronquist K, Acquaviva C, Hutchin T, Rodriguez-Pombo P, Vaisanen ML, Spector E, Creadon-Swindell G, Bras-Goldberg AM, Rahikkala E, Moilanen JS, Mahieu V, Matthijs G, Bravo-Alonso I, Perez-Cerda C, Ugarte M, Vianey-Saban C, Scharer GH, Van Hove JL. The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT. Genet Med. 2017 Jan;19(1):104-111. doi: 10.1038/gim.2016.74. Epub 2016 Jun 30. Erratum In: Genet Med. 2018 Sep;20(9):1098. doi: 10.1038/gim.2017.232. Citation on PubMed
  • Dinopoulos A, Matsubara Y, Kure S. Atypical variants of nonketotic hyperglycinemia. Mol Genet Metab. 2005 Sep-Oct;86(1-2):61-9. doi: 10.1016/j.ymgme.2005.07.016. Citation on PubMed
  • Kikuchi G, Motokawa Y, Yoshida T, Hiraga K. Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia. Proc Jpn Acad Ser B Phys Biol Sci. 2008;84(7):246-63. doi: 10.2183/pjab.84.246. Citation on PubMed or Free article on PubMed Central
  • Kure S, Kato K, Dinopoulos A, Gail C, DeGrauw TJ, Christodoulou J, Bzduch V, Kalmanchey R, Fekete G, Trojovsky A, Plecko B, Breningstall G, Tohyama J, Aoki Y, Matsubara Y. Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia. Hum Mutat. 2006 Apr;27(4):343-52. doi: 10.1002/humu.20293. Citation on PubMed
  • Nakai T, Nakagawa N, Maoka N, Masui R, Kuramitsu S, Kamiya N. Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia. EMBO J. 2005 Apr 20;24(8):1523-36. doi: 10.1038/sj.emboj.7600632. Epub 2005 Mar 24. Citation on PubMed or Free article on PubMed Central
  • Sellner L, Edkins E, Greed L, Lewis B. Detection of mutations in the glycine decarboxylase gene in patients with nonketotic hyperglycinaemia. Mol Genet Metab. 2005 Feb;84(2):167-71. doi: 10.1016/j.ymgme.2004.10.001. Epub 2004 Nov 23. Citation on PubMed
  • Swanson MA, Coughlin CR Jr, Scharer GH, Szerlong HJ, Bjoraker KJ, Spector EB, Creadon-Swindell G, Mahieu V, Matthijs G, Hennermann JB, Applegarth DA, Toone JR, Tong S, Williams K, Van Hove JL. Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia. Ann Neurol. 2015 Oct;78(4):606-18. doi: 10.1002/ana.24485. Epub 2015 Aug 10. Erratum In: Ann Neurol. 2016 Mar;79(3):505. doi: 10.1002/ana.24600. Citation on PubMed or Free article on PubMed Central
  • Van Hove JLK, Coughlin C II, Swanson M, Hennermann JB. Nonketotic Hyperglycinemia. 2002 Nov 14 [updated 2019 May 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1357/ Citation on PubMed

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