ピログルタミン酸尿症
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/24 17:12:49」(JST)
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| Glutathione synthetase deficiency |
| Classification and external resources |
Glutathione
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| 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.
Contents
- 1 Diagnosis
- 2 Genetics
- 3 References
- 4 External links
Diagnosis[edit]
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); mental retardation; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections.
Genetics[edit]
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[edit]
- ^ 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.
- ^ a b 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[edit]
- 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.
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Inborn error of amino acid metabolism (E70–E72, 270)
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| K→acetyl-CoA |
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Lysine/straight chain
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- Glutaric acidemia type 1
- type 2
- Hyperlysinemia
- Pipecolic acidemia
- Saccharopinuria
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Leucine
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- 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
- 3-Methylcrotonyl-CoA carboxylase deficiency
- 3-Methylglutaconic aciduria 1
- Isovaleric acidemia
- Maple syrup urine disease
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Tryptophan
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| G |
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G→pyruvate→citrate
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Glycine
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- D-Glyceric acidemia
- Glutathione synthetase deficiency
- Sarcosinemia
- Glycine→Creatine: GAMT deficiency
- Glycine encephalopathy
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G→glutamate→
α-ketoglutarate
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Histidine
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- Carnosinemia
- Histidinemia
- Urocanic aciduria
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Proline
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- Hyperprolinemia
- Prolidase deficiency
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Glutamate/glutamine
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G→propionyl-CoA→
succinyl-CoA
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Valine
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- Hypervalinemia
- Isobutyryl-CoA dehydrogenase deficiency
- Maple syrup urine disease
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Isoleucine
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- 2-Methylbutyryl-CoA dehydrogenase deficiency
- Beta-ketothiolase deficiency
- Maple syrup urine disease
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Methionine
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- Cystathioninuria
- Homocystinuria
- Hypermethioninemia
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General BC/OA
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- Methylmalonic acidemia
- Methylmalonyl-CoA mutase deficiency
- Propionic acidemia
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G→fumarate
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Phenylalanine/tyrosine
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Phenylketonuria
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- 6-Pyruvoyltetrahydropterin synthase deficiency
- Tetrahydrobiopterin deficiency
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Tyrosinemia
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- Alkaptonuria/Ochronosis
- Type I tyrosinemia
- Type II tyrosinemia
- Type III tyrosinemia/Hawkinsinuria
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Tyrosine→Melanin
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- Albinism: Ocular albinism (1)
- Oculocutaneous albinism (Hermansky–Pudlak syndrome)
- Waardenburg syndrome
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Tyrosine→Norepinephrine
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- Dopamine beta hydroxylase deficiency
- reverse: Brunner syndrome
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G→oxaloacetate
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Urea cycle/Hyperammonemia
(arginine
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- Argininemia
- Argininosuccinic aciduria
- Carbamoyl phosphate synthetase I deficiency
- Citrullinemia
- N-Acetylglutamate synthase deficiency
- Ornithine transcarbamylase deficiency/translocase deficiency
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Transport/
IE of RTT |
- Solute carrier family: Cystinuria
- Hartnup disease
- Iminoglycinuria
- Lysinuric protein intolerance
- Fanconi syndrome: Oculocerebrorenal syndrome
- Cystinosis
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| Other |
- 2-Hydroxyglutaric aciduria
- Aminoacylase 1 deficiency
- Ethylmalonic encephalopathy
- Fumarase deficiency
- Trimethylaminuria
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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UpToDate Contents
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English Journal
- Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency.
- Signolet I1, Chenouard R1, Oca F1, Barth M1, Reynier P1, Denis MC1, Simard G2.
- Pediatrics.Pediatrics.2016 Sep;138(3). pii: e20154324. doi: 10.1542/peds.2015-4324.
- Hemolytic anemia (HA) of the newborn should be considered in cases of rapidly developing, severe, or persistent hyperbilirubinemia. Several causes of corpuscular hemolysis have been described, among which red blood cell enzyme defects are of particular concern. We report a rare case of red blood cel
- PMID 27581854
- Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine.
- Gomez-Ospina N1, Scott AI2, Oh GJ3, Potter D3, Goel VV3, Destino L3, Baugh N3, Enns GM3, Niemi AK3, Cowan TM3,2.
- Journal of inherited metabolic disease.J Inherit Metab Dis.2016 Aug 3. [Epub ahead of print]
- Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyr
- PMID 27488560
- Unravelling 5-oxoprolinuria (pyroglutamic aciduria) due to bi-allelic OPLAH mutations: 20 new mutations in 14 families.
- Sass JO1, Gemperle-Britschgi C2, Tarailo-Graovac M3, Patel N4, Walter M5, Jordanova A6, Alfadhel M7, Barić I8, Çoker M9, Damli-Huber A10, Faqeih EA11, García Segarra N12, Geraghty MT13, Jåtun BM14, Kalkan Uçar S9, Kriewitz M15, Rauchenzauner M16, Bilić K17, Tournev I18, Till C19, Sayson B20, Beumer D20, Ye CX5, Zhang LH21, Vallance H22, Alkuraya FS4, van Karnebeek CD21.
- Molecular genetics and metabolism.Mol Genet Metab.2016 Jul 22. pii: S1096-7192(16)30146-9. doi: 10.1016/j.ymgme.2016.07.008. [Epub ahead of print]
- Primary 5-oxoprolinuria (pyroglutamic aciduria) is caused by a genetic defect in the γ-glutamyl cycle, affecting either glutathione synthetase or 5-oxoprolinase. While several dozens of patients with glutathione synthetase deficiency have been reported, with hemolytic anemia representing the clinic
- PMID 27477828
Japanese Journal
- Pyroglutamic aciduria. Studies in an infant with chronic metabolic acidosis.
- Pyroglutamic aciduria-a new inborn error of metabolism.
Related Links
- Pyroglutamic aciduria symptoms, causes, diagnosis, and treatment information for Pyroglutamic aciduria (Glutathione Synthetase Deficiency) with alternative diagnoses, full-text book chapters, misdiagnosis, research treatments ...
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