MCID: GLT007
MIFTS: 43

Glutathione Synthetase Deficiency

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Glutathione Synthetase Deficiency

MalaCards integrated aliases for Glutathione Synthetase Deficiency:

Name: Glutathione Synthetase Deficiency 54 50 24 25 56 71 29 13 52
Pyroglutamic Aciduria 50 24 25 71
5-Oxoprolinuria 50 24 25 71
Pyroglutamicaciduria 50 24 56
Glutathione Synthetase Deficiency with 5-Oxoprolinuria 56
Deficiency of Glutathione Synthetase 25
Deficiency of Glutathione Synthase 25
Gluthathione Synthetase Deficiency 69
5-Oxoprolinase Deficiency 69
Oxoprolinase Deficiency 50
Glutathione Synthetase 13
Pyroglutamic Acidemia 25
5-Oxoprolinemia 25
Gss Deficiency 71

Characteristics:

Orphanet epidemiological data:

56
glutathione synthetase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
glutathione synthetase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Glutathione Synthetase Deficiency

NIH Rare Diseases : 50 glutathione synthetase deficiency is type of organic acidemia that affects the production glutathione. glutathione helps prevent cell damage, build dna and proteins, and process medications and cancer-causing compounds. people can have mild, moderate, or severe disease. mild disease may cause hemolytic anemia and 5-oxoprolinuria (excess excretion of 5-oxoproline in urine). moderate disease may cause anemia, 5-oxoprolinuria, and metabolic acidosis in early infancy. severe disease may cause anemia, 5-oxoprolinuria, metabolic acidosis, neurological symptoms (e.g., seizures, learning disability, loss of coordination), and recurrent infections. it is caused by mutations in the gss gene and is inherited in an autosomal recessive fashion. last updated: 2/4/2011

MalaCards based summary : Glutathione Synthetase Deficiency, also known as pyroglutamic aciduria, is related to hepatitis and hemolytic anemia due to glutathione synthetase deficiency, and has symptoms including hemolytic anemia, chronic metabolic acidosis and abnormality of immune system physiology. An important gene associated with Glutathione Synthetase Deficiency is GSS (Glutathione Synthetase), and among its related pathways/superpathways are Metabolism and Arachidonic acid metabolism. Affiliated tissues include neutrophil and liver.

UniProtKB/Swiss-Prot : 71 Glutathione synthetase deficiency: Severe form characterized by an increased rate of hemolysis and defective function of the central nervous system.

Genetics Home Reference : 25 Glutathione synthetase deficiency is a disorder that prevents the production of an important molecule called glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.

OMIM : 54
Glutathione synthetase deficiency, or 5-oxoprolinuria, is an autosomal recessive disorder characterized, in its severe form, by massive urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia, and central nervous system damage. The metabolic defect results in decreased levels of cellular glutathione, which overstimulates the synthesis of gamma-glutamylcysteine and its subsequent conversion to 5-oxoproline (Larsson and Anderson, 2001). (266130)

Wikipedia : 72 Glutathione synthetase deficiency is a rare autosomal recessivemetabolic disorder that prevents the... more...

Related Diseases for Glutathione Synthetase Deficiency

Diseases related to Glutathione Synthetase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
id Related Disease Score Top Affiliating Genes
1 hepatitis 29.3 G6PD GSS
2 hemolytic anemia due to glutathione synthetase deficiency 12.5
3 hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency 11.2
4 5-oxoprolinase deficiency 11.1
5 hemolytic anemia 10.1
6 metabolic acidosis 9.9
7 cone dystrophy 9.7
8 cerebritis 9.7
9 albinism 9.7
10 tumefactive multiple sclerosis 9.4 ALOX5 GGT1
11 pyelitis 9.4 G6PD GGT1
12 acute erythroid leukemia 8.9 ALOX5 G6PD GGT1
13 aicardi-goutieres syndrome 5 7.5 ALOX5 G6PD GGT1 GLUL GSS OPLAH

Graphical network of the top 20 diseases related to Glutathione Synthetase Deficiency:



Diseases related to Glutathione Synthetase Deficiency

Symptoms & Phenotypes for Glutathione Synthetase Deficiency

Symptoms via clinical synopsis from OMIM:

54

Neuro:
mental retardation
dysarthria
ataxia
seizures
intention tremor
more
Eyes:
peripheral retinal pigmentation abnormalities

Heme:
increased hemolysis
mild hemolytic anemia
episodic neutropenia

Lab:
glutathione synthetase deficiency
pyroglutamic acidemia
pyroglutamic aciduria
decreased erythrocyte glutathione
increased gamma-glutamyl-cysteine synthetase
more
Metabolic:
chronic metabolic acidosis


Clinical features from OMIM:

266130

Human phenotypes related to Glutathione Synthetase Deficiency:

56 32 (show all 14)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hemolytic anemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001878
2 glutathione synthetase deficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0003343
3 chronic metabolic acidosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001996
4 abnormality of immune system physiology 56 32 hallmark (90%) Very frequent (99-80%) HP:0010978
5 abnormality of the nervous system 56 32 hallmark (90%) Very frequent (99-80%) HP:0000707
6 dysarthria 32 HP:0001260
7 ataxia 32 HP:0001251
8 neutropenia 32 HP:0001875
9 seizures 32 HP:0001250
10 pigmentary retinopathy 32 HP:0000580
11 intellectual disability 32 HP:0001249
12 intention tremor 32 HP:0002080
13 spastic tetraparesis 32 HP:0001285
14 psychotic mentation 32 HP:0001345

UMLS symptoms related to Glutathione Synthetase Deficiency:


abdominal pain, diarrhea, vomiting

Drugs & Therapeutics for Glutathione Synthetase Deficiency

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Review of French Cases of Glutathione Synthetase Deficiency Not yet recruiting NCT02830867

Search NIH Clinical Center for Glutathione Synthetase Deficiency

Genetic Tests for Glutathione Synthetase Deficiency

Genetic tests related to Glutathione Synthetase Deficiency:

id Genetic test Affiliating Genes
1 Glutathione Synthetase Deficiency 29 24 GSS

Anatomical Context for Glutathione Synthetase Deficiency

MalaCards organs/tissues related to Glutathione Synthetase Deficiency:

39
Neutrophil, Liver

Publications for Glutathione Synthetase Deficiency

Articles related to Glutathione Synthetase Deficiency:

(show top 50) (show all 53)
id Title Authors Year
1
A Rare Cause of Neonatal Hemolytic Anemia: Glutathione Synthetase Deficiency. ( 28267090 )
2017
2
Clinical findings and effect of sodium hydrogen carbonate in patients with glutathione synthetase deficiency. ( 26669244 )
2016
3
Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency. ( 27581854 )
2016
4
Nineteen-year follow-up of a patient with severe glutathione synthetase deficiency. ( 26984560 )
2016
5
Fundus autofluorescence and optical coherence tomography findings in glutathione synthetase deficiency. ( 25727596 )
2015
6
Hemolytic Anemia and Metabolic Acidosis: Think about Glutathione Synthetase Deficiency. ( 25166299 )
2014
7
Rod-cone dystrophy with maculopathy in genetic glutathione synthetase deficiency: a morphologic and electrophysiologic study. ( 19111905 )
2009
8
Diagnosis of glutathione synthetase deficiency in newborn screening. ( 19728142 )
2009
9
Acetaminophen-induced hepatotoxicity in a glutathione synthetase-deficient patient. ( 17479648 )
2007
10
Oxidative DNA damage in cultured fibroblasts from patients with hereditary glutathione synthetase deficiency. ( 16036337 )
2005
11
Genotype, enzyme activity, glutathione level, and clinical phenotype in patients with glutathione synthetase deficiency. ( 15717202 )
2005
12
Glutathione synthetase deficiency. ( 15990954 )
2005
13
Trial of erythropoietin treatment in a boy with glutathione synthetase deficiency. ( 16435214 )
2005
14
A newborn infant with generalized glutathione synthetase deficiency. ( 15074378 )
2004
15
S-Acetylglutathione normalizes intracellular glutathione content in cultured fibroblasts from patients with glutathione synthetase deficiency. ( 15617191 )
2004
16
Human hereditary glutathione synthetase deficiency: kinetic properties of mutant enzymes. ( 15056072 )
2004
17
Acute metabolic crisis with extreme deficiency of glutathione in combination with decreased levels of leukotriene C4 in a patient with glutathione synthetase deficiency. ( 15243994 )
2004
18
Glutathione synthetase deficiency associated with antenatal cerebral bleeding. ( 15243982 )
2004
19
Diagnostics in patients with glutathione synthetase deficiency but without mutations in the exons of the GSS gene. ( 14635114 )
2003
20
Glutathione synthetase deficiency: is gamma-glutamylcysteine accumulation a way to cope with oxidative stress in cells with insufficient levels of glutathione? ( 12638941 )
2002
21
Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies. ( 11167850 )
2001
22
Long-term clinical outcome in patients with glutathione synthetase deficiency. ( 11445798 )
2001
23
Kinetic properties of missense mutations in patients with glutathione synthetase deficiency. ( 10861239 )
2000
24
Generalized glutathione synthetase deficiency and pregnancy. ( 10472538 )
1999
25
Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. ( 10369661 )
1999
26
Clinical, biochemical, and molecular characterization of patients with glutathione synthetase deficiency. ( 10450861 )
1999
27
[Biochemical and molecular bases of glutathione synthetase deficiency]. ( 9590072 )
1998
28
Effect of decreased glutathione levels in hereditary glutathione synthetase deficiency on dibromoethane-induced genotoxicity in human fibroblasts. ( 9093395 )
1997
29
[Glutathione synthetase deficiency]. ( 8847804 )
1996
30
Tyrosinaemia type 1 and glutathione synthetase deficiency: two disorders with reduced hepatic thiol group concentrations and a liver 4-fumarylacetoacetate hydrolase deficiency. ( 7623442 )
1995
31
Impaired synthesis of lipoxygenase products in glutathione synthetase deficiency. ( 8190517 )
1994
32
Glutathione synthetase deficiency: a family report. ( 8158601 )
1994
33
Effect of ascorbate or N-acetylcysteine treatment in a patient with hereditary glutathione synthetase deficiency. ( 8301428 )
1994
34
High-dose vitamin E therapy in glutathione synthetase deficiency. ( 7707700 )
1994
35
Deficient synthesis of cysteinyl leukotrienes in glutathione synthetase deficiency. ( 8088946 )
1993
36
Prenatal analysis in two suspected cases of glutathione synthetase deficiency. ( 8295398 )
1993
37
5-Oxoprolinuria due to glutathione synthetase deficiency. ( 1293394 )
1992
38
5-Oxoprolinuria (glutathione synthetase deficiency): a case with neonatal presentation and rapid fatal outcome. ( 1770788 )
1991
39
A therapeutic trial with N-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria). ( 2502672 )
1989
40
Erythrocyte glutathione synthetase deficiency leads not only to glutathione but also to glutathione-S-transferase deficiency. ( 3944259 )
1986
41
Sulphur amino-acid degradation in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria). ( 3938407 )
1985
42
Acetaminophen toxicity in lymphocytes heterozygous for glutathione synthetase deficiency. ( 4041989 )
1985
43
Ophthalmological, psychometric and therapeutic investigation in two sisters with hereditary glutathione synthetase deficiency (5-oxoprolinuria). ( 4047346 )
1985
44
Hemolytic anemia, recurrent metabolic acidosis, and incomplete albinism associated with glutathione synthetase deficiency. ( 6882923 )
1983
45
Chronic hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency or glutathione synthetase deficiency: the role of vitamin E in its treatment. ( 6959562 )
1982
46
Pyroglutamic aciduria (5-oxoprolinuria) without glutathione synthetase deficiency and with decreased pyroglutamate hydrolase activity. ( 6790862 )
1981
47
Protection of granulocytes by vitamin E in glutathione synthetase deficiency. ( 481537 )
1979
48
Association of glutathione synthetase deficiency and diminished amino acid transport in yeast. ( 42394 )
1979
49
Oxidative damage to neutrophils in glutathione synthetase deficiency. ( 465367 )
1979
50
Biochemical heterogeneity in glutathione synthetase deficiency. ( 659603 )
1978

Variations for Glutathione Synthetase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Glutathione Synthetase Deficiency:

71 (show all 14)
id Symbol AA change Variation ID SNP ID
1 GSS p.Ala26Asp VAR_003602 rs759253242
2 GSS p.Leu188Pro VAR_003603
3 GSS p.Asp219Ala VAR_003604
4 GSS p.Asp219Gly VAR_003605 rs28938472
5 GSS p.Leu254Arg VAR_003606
6 GSS p.Arg267Trp VAR_003607 rs121909308
7 GSS p.Tyr270Cys VAR_003608
8 GSS p.Tyr270His VAR_003609
9 GSS p.Arg283Cys VAR_003610 rs121909309
10 GSS p.Leu286Gln VAR_003611
11 GSS p.Arg330Cys VAR_003612 rs148640446
12 GSS p.Gly464Val VAR_003613
13 GSS p.Asp469Glu VAR_003614
14 GSS p.Leu301Pro VAR_078567

ClinVar genetic disease variations for Glutathione Synthetase Deficiency:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 GSS NM_000178.3(GSS): c.491G> A (p.Arg164Gln) single nucleotide variant Pathogenic rs121909307 GRCh37 Chromosome 20, 33530291: 33530291
2 GSS GSS, 1-BP DEL, NT3/4G deletion Pathogenic
3 GSS NM_000178.3(GSS): c.799C> T (p.Arg267Trp) single nucleotide variant Pathogenic rs121909308 GRCh37 Chromosome 20, 33523414: 33523414
4 GSS NM_000178.3(GSS): c.847C> T (p.Arg283Cys) single nucleotide variant Pathogenic rs121909309 GRCh37 Chromosome 20, 33519924: 33519924
5 GSS NM_000178.3(GSS): c.373C> T (p.Arg125Cys) single nucleotide variant Pathogenic rs28936396 GRCh37 Chromosome 20, 33530409: 33530409

Expression for Glutathione Synthetase Deficiency

Search GEO for disease gene expression data for Glutathione Synthetase Deficiency.

Pathways for Glutathione Synthetase Deficiency

Pathways related to Glutathione Synthetase Deficiency according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.36 ALOX5 G6PD GGT1 GLUL GSS OPLAH
2
Show member pathways
11.65 ALOX5 GGT1
3 11.57 G6PD GGT1
4
Show member pathways
11.43 ALOX5 GGT1
5 11.28 GLUL GSS
6
Show member pathways
11.23 G6PD GGT1 GSS OPLAH
7 10.54 ALOX5 GGT1
8 9.86 ALOX5 GGT1

GO Terms for Glutathione Synthetase Deficiency

Biological processes related to Glutathione Synthetase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cellular amino acid metabolic process GO:0006520 9.32 GGT1 GSS
2 glutamate metabolic process GO:0006536 9.26 GGT1 GLUL
3 leukotriene metabolic process GO:0006691 9.16 ALOX5 GGT1
4 glutathione metabolic process GO:0006749 8.96 G6PD GGT1
5 glutathione biosynthetic process GO:0006750 8.8 GGT1 GSS OPLAH

Molecular functions related to Glutathione Synthetase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 ligase activity GO:0016874 8.62 GLUL GSS

Sources for Glutathione Synthetase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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