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Glycine encephalopathy(NKH; GCE1)

MedGen UID:
155625
Concept ID:
C0751748
Disease or Syndrome
Synonyms: AMT-Related Glycine Encephalopathy; GLDC-Related Glycine Encephalopathy; Non-ketotic hyperglycinemia; Nonketotic hyperglycinemia
SNOMED CT: Non ketotic hyperglycinemia (237939006); Disorder of glycine cleavage enzyme complex (237939006); NKH - Non-ketotic hyperglycinemia (237939006); Non-ketotic hyperglycinemia (237939006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Genes (locations): AMT (3p21.31); GLDC (9p24.1)
 
HPO: HP:0008288
Monarch Initiative: MONDO:0011612
OMIM®: 238300; 605899
OMIM® Phenotypic series: PS605899
Orphanet: ORPHA407

Authors:

Additional description

From MedlinePlus Genetics
Nonketotic hyperglycinemia is a disorder characterized by abnormally high levels of a molecule called glycine in the body (hyperglycinemia). The excess glycine builds up in tissues and organs, particularly the brain. Affected individuals have serious neurological problems.

Nonketotic hyperglycinemia has two forms, the severe form and the attenuated form. Both forms usually begin shortly after birth, although in some cases, signs and symptoms can begin in the first few months of life. Only the attenuated form begins later in infancy. The forms are distinguished by the seriousness of the signs and symptoms. Severe nonketotic hyperglycinemia is more common. Affected babies experience extreme sleepiness (lethargy) that worsens over time and can lead to coma. They can also have weak muscle tone (hypotonia) and life-threatening breathing problems in the first days or weeks of life. Most children who survive these early signs and symptoms develop feeding difficulties, abnormal muscle stiffness (spasticity), profound intellectual disability and seizures that are difficult to control. Most affected children do not achieve normal developmental milestones, such as drinking from a bottle, sitting up, or grabbing objects, and they may lose any acquired skills over time.

The signs and symptoms of the attenuated form of nonketotic hyperglycinemia are similar to, but milder than, those of the severe form of the condition. Children with attenuated nonketotic hyperglycinemia typically reach developmental milestones, although the skills they achieve vary widely. Despite delayed development, many affected children eventually learn to walk and are able to interact with others, often using sign language. Some affected children develop seizures; if present, seizures are usually mild and can be treated. Other features can include spasticity, involuntary jerking movements (chorea), or hyperactivity.

Individuals with nonketotic hyperglycinemia can also have certain changes in the brain, which can be seen using magnetic resonance imaging (MRI). For example, in children with the severe form of the condition, the tissue that connects the left and right halves of the brain (the corpus callosum) is smaller than average.  https://medlineplus.gov/genetics/condition/nonketotic-hyperglycinemia

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGlycine encephalopathy
Follow this link to review classifications for Glycine encephalopathy in Orphanet.

Conditions with this feature

D-Glyceric aciduria
MedGen UID:
452447
Concept ID:
C0342765
Disease or Syndrome
D-glyceric aciduria is a rare autosomal recessive metabolic disorder with a highly variable phenotype. Some patients have an encephalopathic presentation, with severely impaired intellectual development, seizures, microcephaly, and sometimes early death, whereas others have a mild phenotype with only mild speech delay or even normal development (summary by Sass et al., 2010).
Glycine encephalopathy 2
MedGen UID:
1841195
Concept ID:
C5830559
Disease or Syndrome
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).

Professional guidelines

PubMed

Zou W, Li M, Wang X, Lu H, Hao Y, Chen D, Zhu S, Ji D, Zhang Z, Zhou P, Cao Y
J Assist Reprod Genet 2024 May;41(5):1245-1259. Epub 2024 Mar 12 doi: 10.1007/s10815-024-03057-1. PMID: 38470552Free PMC Article
Mastrangelo M
Metab Brain Dis 2021 Jan;36(1):29-43. Epub 2020 Oct 23 doi: 10.1007/s11011-020-00635-x. PMID: 33095372
N Engl J Med 1982 Jun 10;306(23):1425-7. doi: 10.1056/NEJM198206103062316. PMID: 6804868

Recent clinical studies

Etiology

Zou W, Li M, Wang X, Lu H, Hao Y, Chen D, Zhu S, Ji D, Zhang Z, Zhou P, Cao Y
J Assist Reprod Genet 2024 May;41(5):1245-1259. Epub 2024 Mar 12 doi: 10.1007/s10815-024-03057-1. PMID: 38470552Free PMC Article
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
Kuseyri Hübschmann O, Juliá-Palacios NA, Olivella M, Guder P, Zafeiriou DI, Horvath G, Kulhánek J, Pearson TS, Kuster A, Cortès-Saladelafont E, Ibáñez S, García-Jiménez MC, Honzík T, Santer R, Jeltsch K, Garbade SF, Hoffmann GF, Opladen T, García-Cazorla Á
Ann Neurol 2022 Aug;92(2):292-303. Epub 2022 Jun 16 doi: 10.1002/ana.26423. PMID: 35616651
Pearl PL, Taylor JL, Trzcinski S, Sokohl A
J Child Neurol 2007 May;22(5):606-16. doi: 10.1177/0883073807302619. PMID: 17690069
Korman SH, Gutman A
Dev Med Child Neurol 2002 Oct;44(10):712-20. doi: 10.1017/s0012162201002808. PMID: 12418798

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
Lim YT, Mankad K, Kinali M, Tan AP
Neuropediatrics 2020 Feb;51(1):6-21. Epub 2019 Oct 21 doi: 10.1055/s-0039-1698422. PMID: 31634934
Applegarth DA, Toone JR
Am J Med Genet A 2006 Jan 15;140(2):186-8. doi: 10.1002/ajmg.a.31030. PMID: 16353254
Applegarth DA, Toone JR
J Inherit Metab Dis 2004;27(3):417-22. doi: 10.1023/b:boli.0000031222.38328.59. PMID: 15272469
Korman SH, Gutman A
Dev Med Child Neurol 2002 Oct;44(10):712-20. doi: 10.1017/s0012162201002808. PMID: 12418798

Therapy

Dutta D, Majumder M, Paidi RK, Pahan K
Neurobiol Dis 2021 Jun;153:105318. Epub 2021 Feb 24 doi: 10.1016/j.nbd.2021.105318. PMID: 33636386Free PMC Article
Hoover-Fong JE, Shah S, Van Hove JL, Applegarth D, Toone J, Hamosh A
Neurology 2004 Nov 23;63(10):1847-53. doi: 10.1212/01.wnl.0000144270.83080.29. PMID: 15557500
Korman SH, Gutman A
Dev Med Child Neurol 2002 Oct;44(10):712-20. doi: 10.1017/s0012162201002808. PMID: 12418798
Sankaran K, Casey RE, Zaleski WA, Mendelson IM
Clin Pediatr (Phila) 1982 Oct;21(10):636-7. doi: 10.1177/000992288202101015. PMID: 7116748
Melançon SB, Dallaire L, Vincelette P, Potier M, Geoffroy G
Prog Clin Biol Res 1979;34:217-29. PMID: 531053

Prognosis

Kuseyri Hübschmann O, Juliá-Palacios NA, Olivella M, Guder P, Zafeiriou DI, Horvath G, Kulhánek J, Pearson TS, Kuster A, Cortès-Saladelafont E, Ibáñez S, García-Jiménez MC, Honzík T, Santer R, Jeltsch K, Garbade SF, Hoffmann GF, Opladen T, García-Cazorla Á
Ann Neurol 2022 Aug;92(2):292-303. Epub 2022 Jun 16 doi: 10.1002/ana.26423. PMID: 35616651
Mademont-Soler I, Casellas-Vidal D, Trujillo A, Espuña-Capote N, Maroto A, García-González MDM, Ruiz MD, Diego-Álvarez D, Queralt X, Perapoch J, Obón M
Am J Med Genet A 2021 Feb;185(2):476-485. Epub 2020 Dec 2 doi: 10.1002/ajmg.a.61996. PMID: 33269555
Eidi M, Garshasbi M
BMC Neurol 2019 Jul 6;19(1):153. doi: 10.1186/s12883-019-1387-2. PMID: 31279336Free PMC Article
Dulac O
Handb Clin Neurol 2013;113:1785-97. doi: 10.1016/B978-0-444-59565-2.00048-4. PMID: 23622401
Korman SH, Gutman A
Dev Med Child Neurol 2002 Oct;44(10):712-20. doi: 10.1017/s0012162201002808. PMID: 12418798

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
Kuseyri Hübschmann O, Juliá-Palacios NA, Olivella M, Guder P, Zafeiriou DI, Horvath G, Kulhánek J, Pearson TS, Kuster A, Cortès-Saladelafont E, Ibáñez S, García-Jiménez MC, Honzík T, Santer R, Jeltsch K, Garbade SF, Hoffmann GF, Opladen T, García-Cazorla Á
Ann Neurol 2022 Aug;92(2):292-303. Epub 2022 Jun 16 doi: 10.1002/ana.26423. PMID: 35616651
Mademont-Soler I, Casellas-Vidal D, Trujillo A, Espuña-Capote N, Maroto A, García-González MDM, Ruiz MD, Diego-Álvarez D, Queralt X, Perapoch J, Obón M
Am J Med Genet A 2021 Feb;185(2):476-485. Epub 2020 Dec 2 doi: 10.1002/ajmg.a.61996. PMID: 33269555
Hennermann JB, Berger JM, Grieben U, Scharer G, Van Hove JL
J Inherit Metab Dis 2012 Mar;35(2):253-61. Epub 2011 Oct 15 doi: 10.1007/s10545-011-9398-1. PMID: 22002442
Kish SJ, Dixon LM, Burnham WM, Perry TL, Becker L, Cheng J, Chang LJ, Rebbetoy M
Ann Neurol 1988 Sep;24(3):458-61. doi: 10.1002/ana.410240319. PMID: 2906530

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