Glutathione synthetase deficiency

Glutathione synthetase deficiency
Glutathione
Classification and external resources
OMIM	266130
DiseasesDB	29839
eMedicine	ped/867

Glutathione synthetase deficiency is a rare autosomal recessive^[1] metabolic disorder that prevents the production of 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.

Diagnosis

Glutathione synthetase deficiency can be classified into three types: mild, moderate and severe.^[2]

Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). Rarely, affected people also excrete large amounts of a compound called 5-oxoproline (also called pyroglutamic acid, or pyroglutamate) in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells.^[2]
Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis).
In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); intellectual disability; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections.[citation missing]

Genetics

Glutathione synthetase deficiency has an autosomal recessive pattern of inheritance.

Mutations in the GSS gene cause glutathione synthetase deficiency. This gene provides instructions for making the enzyme glutathione synthetase. This enzyme is involved in a process called the gamma-glutamyl cycle, which takes place in most of the body's cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules which are byproducts of energy production. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency.

This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder each carry one copy of the defective gene, but usually are not affected by the disorder.

References

↑ Njålsson, Runa; Ristoff, Ellinor; Carlsson, Katarina; Winkler, Andreas; Larsson, Agne; Norgren, Svante (2005). "Genotype, enzyme activity, glutathione level, and clinical phenotype in patients with glutathione synthetase deficiency". Human Genetics 116 (5): 384–9. doi:10.1007/s00439-005-1255-6. PMID 15717202.
1 2 Njålsson, R. (2005). "Glutathione synthetase deficiency". Cellular and Molecular Life Sciences 62 (17): 1938–45. doi:10.1007/s00018-005-5163-7. PMID 15990954.

External links

Glutathione synthetase deficiency at NLM Genetics Home Reference
Beutler, E; Gelbart, T; Pegelow, C (1986). "Erythrocyte glutathione synthetase deficiency leads not only to glutathione but also to glutathione-S-transferase deficiency". Journal of Clinical Investigation 77 (1): 38–41. doi:10.1172/JCI112298. PMC 423305. PMID 3944259.
The Benefits Of Glutathione Riboceine

Inborn error of amino acid metabolism (E70–E72, 270)

K→acetyl-CoA

Lysine/straight chain	Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria

Leucine	3-hydroxy-3-methylglutaryl-CoA lyase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease

Tryptophan	Hypertryptophanemia

G→pyruvate→citrate

Glycine	D-Glyceric acidemia Glutathione synthetase deficiency Sarcosinemia Glycine→Creatine: GAMT deficiency Glycine encephalopathy

G→glutamate→
α-ketoglutarate

Histidine	Carnosinemia Histidinemia Urocanic aciduria

Proline	Hyperprolinemia Prolidase deficiency

Glutamate/glutamine	SSADHD

G→propionyl-CoA→
succinyl-CoA

Valine	Hypervalinemia Isobutyryl-CoA dehydrogenase deficiency Maple syrup urine disease

Isoleucine	2-Methylbutyryl-CoA dehydrogenase deficiency Beta-ketothiolase deficiency Maple syrup urine disease

Methionine	Cystathioninuria Homocystinuria Hypermethioninemia

General BC/OA	Methylmalonic acidemia Methylmalonyl-CoA mutase deficiency Propionic acidemia

G→fumarate

Phenylalanine/tyrosine

Phenylketonuria	6-Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency

Tyrosinemia	Alkaptonuria/Ochronosis Type I tyrosinemia Type II tyrosinemia Type III tyrosinemia/Hawkinsinuria

Tyrosine→Melanin	Albinism: Ocular albinism (1) Oculocutaneous albinism (Hermansky–Pudlak syndrome) Waardenburg syndrome

Tyrosine→Norepinephrine	Dopamine beta hydroxylase deficiency reverse: Brunner syndrome

G→oxaloacetate

Urea cycle/Hyperammonemia (arginine aspartate)	Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N-Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency/translocase deficiency

Transport/
IE of RTT

Other

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