U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Glycine encephalopathy 2(GCE2)

MedGen UID:
1841195
Concept ID:
C5830559
Disease or Syndrome
Synonym: GCE2
 
Gene (location): AMT (3p21.31)
 
Monarch Initiative: MONDO:0958192
OMIM®: 620398

Definition

Glycine encephalopathy (GCE), also called nonketotic hyperglycinemia (NKH), is an inborn error of metabolism characterized by accumulation of a large amount of glycine in body fluids. Typical cases have severe neurologic features, including seizures, lethargy, and muscular hypotonia soon after birth, and most die with the neonatal period; atypical cases have later onset and less severe psychomotor development (summary by Nanao et al., 1994). For a general description and a discussion of genetic heterogeneity of glycine encephalopathy, see GCE1 (605899). [from OMIM]

Clinical features

From HPO
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
EEG with burst suppression
MedGen UID:
369943
Concept ID:
C1969156
Finding
The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes.
Mild global developmental delay
MedGen UID:
861405
Concept ID:
C4012968
Finding
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
Increased CSF glycine concentration
MedGen UID:
1691638
Concept ID:
C5139615
Finding
Abnormally increased levels of glycine in cerebrospinal fluid.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Non-ketotic hyperglycinemia
MedGen UID:
155625
Concept ID:
C0751748
Disease or Syndrome
Nonketotic hyperglycinemia (NKH) is the inborn error of glycine metabolism defined by deficient activity of the glycine cleavage enzyme system (GCS), which results in accumulation of large quantities of glycine in all body tissues including the brain. Based on ultimate outcome NKH is categorized into severe NKH (no developmental progress and intractable epilepsy) and attenuated NKH (variable developmental progress and treatable or no epilepsy). The majority of children with NKH have onset in the neonatal period manifest as progressive lethargy evolving into profound coma and marked hypotonia; 85% have severe NKH and 15% attenuated NKH. Those with onset between two weeks and three months typically present with hypotonia; 50% have severe NKH and 50% attenuated NKH. Those with onset after age three months have attenuated NKH. Severe versus attenuated NKH is consistent within families, but the degree of developmental progress in those with attenuated NKH can vary.

Professional guidelines

PubMed

Appavu B, Vanatta L, Condie J, Kerrigan JF, Jarrar R
Seizure 2016 Oct;41:62-5. Epub 2016 Jul 21 doi: 10.1016/j.seizure.2016.07.006. PMID: 27475280
Boneh A, Allan S, Mendelson D, Spriggs M, Gillam LH, Korman SH
Mol Genet Metab 2008 Jun;94(2):143-7. Epub 2008 Apr 18 doi: 10.1016/j.ymgme.2008.02.010. PMID: 18395481
Wang PJ, Lee WT, Hwu WL, Young C, Yau KI, Shen YZ
Brain Dev 1998 Oct;20(7):530-5. doi: 10.1016/s0387-7604(98)00042-4. PMID: 9840674

Recent clinical studies

Etiology

Bayrak H, Yıldız Y, Olgaç A, Kasapkara ÇS, Küçükcongar A, Zenciroğlu A, Yüksel D, Ceylaner S, Kılıç M
Metab Brain Dis 2021 Aug;36(6):1213-1222. Epub 2021 Apr 1 doi: 10.1007/s11011-021-00718-3. PMID: 33791923
Mohammad SA, Abdelkhalek HS
Neuroradiology 2017 Nov;59(11):1155-1163. Epub 2017 Sep 1 doi: 10.1007/s00234-017-1913-0. PMID: 28864914
Baysal-Kirac L, Tuzun E, Altindag E, Ekizoglu E, Kinay D, Bilgic B, Tekturk P, Baykan B
Clin EEG Neurosci 2016 Jul;47(3):224-34. Epub 2015 Aug 2 doi: 10.1177/1550059415595907. PMID: 26240088
Carvajal-González A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, Lang B, Pettingill P, Carr A, Sheerin UM, Press R, Press R, Lunn MP, Lim M, Maddison P, Meinck HM, Vandenberghe W, Vincent A
Brain 2014 Aug;137(Pt 8):2178-92. Epub 2014 Jun 20 doi: 10.1093/brain/awu142. PMID: 24951641Free PMC Article
Kikuchi G, Motokawa Y, Yoshida T, Hiraga K
Proc Jpn Acad Ser B Phys Biol Sci 2008;84(7):246-63. doi: 10.2183/pjab.84.246. PMID: 18941301Free PMC Article

Diagnosis

Leyne E, Anselem O, Jordan P, Vivanti AJ, Benachi A, Salomon L, Jacquier M, Jouannic JM, Dhombres F, Cambier T, Rosenblatt J, Pannier E, Goffinet F, Tsatsaris V, Athiel Y
Acta Obstet Gynecol Scand 2024 Jan;103(1):51-58. Epub 2023 Nov 9 doi: 10.1111/aogs.14716. PMID: 37942915Free PMC Article
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
Ann Neurol 2015 Oct;78(4):606-18. Epub 2015 Aug 10 doi: 10.1002/ana.24485. PMID: 26179960Free PMC Article
Leuzzi V, Mastrangelo M, Battini R, Cioni G
Epilepsia 2013 Feb;54(2):217-27. Epub 2012 Nov 13 doi: 10.1111/epi.12020. PMID: 23157605
Ondo WG
Handb Clin Neurol 2011;100:287-91. doi: 10.1016/B978-0-444-52014-2.00021-5. PMID: 21496588
Biasioli S, D'Andrea G, Feriani M, Chiaramonte S, Fabris A, Ronco C, La Greca G
Clin Nephrol 1986 Feb;25(2):57-63. PMID: 3516476

Therapy

Gupta J, Badal S, Anand V, Jauhari P, Chakrabarty B, Gulati S
Neurol India 2022 Jan-Feb;70(1):312-314. doi: 10.4103/0028-3886.338670. PMID: 35263902
Stein J, Boehles HJ, Blumenstein I, Goeters C, Schulz R; Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine
Ger Med Sci 2009 Nov 18;7:Doc24. doi: 10.3205/000083. PMID: 20049071Free PMC Article
Chen PT, Young C, Lee WT, Wang PJ, Peng SS, Shen YZ
Brain Dev 2001 Nov;23(7):715-20. doi: 10.1016/s0387-7604(01)00285-6. PMID: 11701284
Deutsch SI, Rosse RB, Mastropaolo J
Clin Neuropharmacol 1998 Mar-Apr;21(2):71-9. PMID: 9579291
Zieve L
J Am Coll Nutr 1986;5(2):167-76. doi: 10.1080/07315724.1986.10720123. PMID: 3088083

Prognosis

Gupta J, Badal S, Anand V, Jauhari P, Chakrabarty B, Gulati S
Neurol India 2022 Jan-Feb;70(1):312-314. doi: 10.4103/0028-3886.338670. PMID: 35263902
Bayrak H, Yıldız Y, Olgaç A, Kasapkara ÇS, Küçükcongar A, Zenciroğlu A, Yüksel D, Ceylaner S, Kılıç M
Metab Brain Dis 2021 Aug;36(6):1213-1222. Epub 2021 Apr 1 doi: 10.1007/s11011-021-00718-3. PMID: 33791923
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
Ann Neurol 2015 Oct;78(4):606-18. Epub 2015 Aug 10 doi: 10.1002/ana.24485. PMID: 26179960Free PMC Article
Carvajal-González A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, Lang B, Pettingill P, Carr A, Sheerin UM, Press R, Press R, Lunn MP, Lim M, Maddison P, Meinck HM, Vandenberghe W, Vincent A
Brain 2014 Aug;137(Pt 8):2178-92. Epub 2014 Jun 20 doi: 10.1093/brain/awu142. PMID: 24951641Free PMC Article
Schiffmann R, Kaye EM, Willis JK 3rd, Africk D, Ampola M
Ann Neurol 1989 Feb;25(2):201-3. doi: 10.1002/ana.410250218. PMID: 2919871

Clinical prediction guides

Leyne E, Anselem O, Jordan P, Vivanti AJ, Benachi A, Salomon L, Jacquier M, Jouannic JM, Dhombres F, Cambier T, Rosenblatt J, Pannier E, Goffinet F, Tsatsaris V, Athiel Y
Acta Obstet Gynecol Scand 2024 Jan;103(1):51-58. Epub 2023 Nov 9 doi: 10.1111/aogs.14716. PMID: 37942915Free PMC Article
Gupta J, Badal S, Anand V, Jauhari P, Chakrabarty B, Gulati S
Neurol India 2022 Jan-Feb;70(1):312-314. doi: 10.4103/0028-3886.338670. PMID: 35263902
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
Ann Neurol 2015 Oct;78(4):606-18. Epub 2015 Aug 10 doi: 10.1002/ana.24485. PMID: 26179960Free PMC Article
Carvajal-González A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, Lang B, Pettingill P, Carr A, Sheerin UM, Press R, Press R, Lunn MP, Lim M, Maddison P, Meinck HM, Vandenberghe W, Vincent A
Brain 2014 Aug;137(Pt 8):2178-92. Epub 2014 Jun 20 doi: 10.1093/brain/awu142. PMID: 24951641Free PMC Article
Boneh A, Allan S, Mendelson D, Spriggs M, Gillam LH, Korman SH
Mol Genet Metab 2008 Jun;94(2):143-7. Epub 2008 Apr 18 doi: 10.1016/j.ymgme.2008.02.010. PMID: 18395481

Recent systematic reviews

Lora-Tamayo J, Palom X, Sarrá J, Gasch O, Isern V, Fernández de Sevilla A, Pujol R
Clin Lymphoma Myeloma 2008 Dec;8(6):363-9. doi: 10.3816/CLM.2008.n.054. PMID: 19064403

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...