Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

Gamma-glutamylcysteine synthetase deficiency

MedGen UID:: 347272
•Concept ID:: C1856603
•: Disease or Syndrome

Synonym:	Gamma-glutamylcysteine synthetase deficiency, hemolytic anemia due to
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). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	GCLC (6p12.1)

Monarch Initiative:	MONDO:0009259
OMIM®:	230450
Orphanet:	ORPHA33574

Definition

Gamma-glutamylcysteine synthetase deficiency is 1 of 4 diseases involving enzymes in the gamma-glutamyl cycle (Meister, 1974). The other 3 disorders are glutathione synthetase deficiency (231900), 5-oxoprolinuria, which is a severe or generalized form of glutathione synthetase deficiency (266130), and gamma-glutamyl transpeptidase deficiency (231950). All except gamma-glutamyl transpeptidase deficiency are accompanied by hemolytic anemia (Larsson and Anderson, 2001). [from OMIM]

Clinical features

From HPO

Polyneuropathy

MedGen UID:: 57502
•Concept ID:: C0152025
•: Disease or Syndrome

A generalized disorder of peripheral nerves.

See: Feature record | Search on this feature

Late-onset spinocerebellar degeneration

MedGen UID:: 347273
•Concept ID:: C1856604
•: Finding

See: Feature record | Search on this feature

Hemolytic anemia

MedGen UID:: 1916
•Concept ID:: C0002878
•: Disease or Syndrome

A type of anemia caused by premature destruction of red blood cells (hemolysis).

See: Feature record | Search on this feature

Reticulocytosis

MedGen UID:: 60089
•Concept ID:: C0206160
•: Finding

An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.

See: Feature record | Search on this feature

Myopathy

MedGen UID:: 10135
•Concept ID:: C0026848
•: Disease or Syndrome

A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.

See: Feature record | Search on this feature

Increased circulating lactate dehydrogenase concentration

MedGen UID:: 1377250
•Concept ID:: C4477095
•: Finding

An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

See: Feature record | Search on this feature

Reduced erythrocyte gamma-glutamyl cysteine synthetase activity

MedGen UID:: 1052439
•Concept ID:: CN376641
•: Finding

Activity of gamma-glutamylcysteine synthetase (EC 6.3.2.2) in erythrocytes below the lower limit of normal.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of blood and blood-forming tissues
- Hemolytic anemia
- Reticulocytosis
Abnormality of metabolism/homeostasis
- Increased circulating lactate dehydrogenase concentration
- Reduced erythrocyte gamma-glutamyl cysteine synthetase activity
Abnormality of the musculoskeletal system
- Myopathy
Abnormality of the nervous system
- Late-onset spinocerebellar degeneration
- Polyneuropathy

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVGamma-glutamylcysteine synthetase deficiency

Hemolytic anemia due to hexose monophosphate shunt and glutathione metabolism anomalies
- Gamma-glutamylcysteine synthetase deficiency

Follow this link to review classifications for Gamma-glutamylcysteine synthetase deficiency in Orphanet.

Professional guidelines

PubMed

Induction of glutathione biosynthesis by glycine-based treatment mitigates atherosclerosis.

Rom O, Liu Y, Finney AC, Ghrayeb A, Zhao Y, Shukha Y, Wang L, Rajanayake KK, Das S, Rashdan NA, Weissman N, Delgadillo L, Wen B, Garcia-Barrio MT, Aviram M, Kevil CG, Yurdagul A Jr, Pattillo CB, Zhang J, Sun D, Hayek T, Gottlieb E, Mor I, Chen YE
Redox Biol 2022 Jun;52:102313. Epub 2022 Apr 13 doi: 10.1016/j.redox.2022.102313. PMID: 35447412 Free PMC Article

Genotype, enzyme activity, glutathione level, and clinical phenotype in patients with glutathione synthetase deficiency.

Njålsson R, Ristoff E, Carlsson K, Winkler A, Larsson A, Norgren S
Hum Genet 2005 Apr;116(5):384-9. Epub 2005 Feb 17 doi: 10.1007/s00439-005-1255-6. PMID: 15717202

See all (2)

Recent clinical studies

Diagnosis

Chronic non-spherocytic hemolytic anemia associated with severe neurological disease due to gamma-glutamylcysteine synthetase deficiency in a patient of Moroccan origin.

Mañú Pereira M, Gelbart T, Ristoff E, Crain KC, Bergua JM, López Lafuente A, Kalko SG, García Mateos E, Beutler E, Vives Corrons JL
Haematologica 2007 Nov;92(11):e102-5. doi: 10.3324/haematol.11238. PMID: 18024385

Inborn errors in the metabolism of glutathione.

Ristoff E, Larsson A
Orphanet J Rare Dis 2007 Mar 30;2:16. doi: 10.1186/1750-1172-2-16. PMID: 17397529 Free PMC Article

See all (2)