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| Ornithine transcarbamylase deficiency |
| Classification and external resources |
Ornithine |
| ICD-10 |
E72.4 |
| ICD-9 |
270.6 |
| OMIM |
311250 |
| DiseasesDB |
9286 |
| MedlinePlus |
000372 |
| eMedicine |
ped/2744 |
| MeSH |
D020163 |
Ornithine transcarbamylase deficiency (OTCD), a common urea cycle disorder, is a rare metabolic disorder, occurring in one out of every 80,000 births. OTCD is a genetic disorder resulting in a mutated and ineffective form of the enzyme ornithine transcarbamylase.
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Contents
- 1 Symptoms
- 2 Genetics
- 3 Treatment
- 4 References
- 5 External links
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Symptoms
Like other urea cycle disorders, OTC affects the body's ability to get rid of ammonia, a toxic breakdown product of the body's use of protein. As a result, ammonia accumulates in the blood causing hyperammonemia. This ammonia travels to the various organs of the body.
Another symptom of OTC is a buildup of orotic acid in the blood. This is due to an anapleurosis that occurs with carbamoyl phosphate entering the pyrimidine synthesis pathway.
Ornithine transcarbamylase deficiency often becomes evident in the first few days of life, however it can present at middle age.[1] An infant with ornithine transcarbamylase deficiency may be lacking in energy (lethargic) or unwilling to eat, and have poorly-controlled breathing rate or body temperature. Some babies with this disorder may experience seizures or unusual body movements, or go into a coma. In cases where OTC enzyme production is low or non-existent, death can occur within the first days of life. Complications from ornithine transcarbamylase deficiency may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen. Other symptoms include irrational behavior (caused by encephalitis), mood swings, and poor performance in school.
In some affected individuals, signs and symptoms of ornithine transcarbamylase may be less severe, and may not appear until later in life. Some female carriers become symptomatic later in life in times of metabolic stress. This can happen as a result of anorexia, starvation, malnutrition, pregnancy or even (in at least one case) as a result of gastric bypass surgery. It is also possible for symptoms to be exacerbated by extreme trauma of many sorts, including, (at least in one case) adolescent pregnancy coupled with severe stomach flu.
Genetics
Ornithine transcarbamylase deficiency is an X-linked recessive disorder caused by a number of different mutations in the OTC gene. Since the gene is on the X chromosome, females are primarily carriers while males with nonconservative mutations rarely survive past 72 hours of birth. Half of those survivors die in the first month, and half of the remaining by age 5. Prognosis is less clear in cases of adult onset OTCD, as detection of the disease is almost universally post symptomatic.[2]
Treatment
Since the disease results in an inability to handle large amounts of nitrogen load, the treatment includes strategies to decrease the intake of nitrogen (low-protein diet), prevention of excessive body protein breakdown during acute illnesses (hydration and nutrition) and administration of medications scavenging nitrogen (sodium benzoate and sodium phenylbutyrate). Some patients may need to have supplemental amino acids (arginine, citrulline, valine, leucine, isoleucine). Arginine in particular may be useful due to its role in the urea cycle, but it is also pro-viral and excess nitric oxide (which is synthesized from arginine) can be problematic[citation needed]. Biotin may also be useful due to its stimulatory effect on the ornithine transcarbamylase enzyme [3] and its reported ability to reduce ammonia levels in experimental animal studies.[4]
In cases where the OTC enzyme production is very low or non-existent and treatment consisting of low-protein diet and dietary supplementation are inadequate, liver transplant may become a treatment option.
New efforts to combat the illness starts with prenatal treatment to protect the fetus which has been identified with OTC deficiency through amniocentesis. There is a case report of success using this approach.[5]
References
- ^ Ornithine transcarbamylase deficiency at eMedicine
- ^ Ornithine transcarbamylase deficiency~followup at eMedicine
- ^ Maeda, Y; Kawata, S; Inui, Y; Fukuda, K; Igura, T; Matsuzawa, Y (1996). "Biotin deficiency decreases ornithine transcarbamylase activity and mRNA in rat liver". The Journal of nutrition 126 (1): 61–6. PMID 8558326.
- ^ Nagamine, T; Saito, S; Kaneko, M; Sekiguchi, T; Sugimoto, H; Takehara, K; Takagi, H (1995). "Effect of biotin on ammonia intoxication in rats and mice". Journal of gastroenterology 30 (3): 351–5. PMID 7647902.
- ^ http://med.stanford.edu/ism/2010/april/enns-0426.html
- National Library of Medicine Ornithine transcarbamylase deficiency
External links
- GeneReviews/NCBI/NIH/UW entry on Urea Cycle Disorders Overview
- http://www.nucdf.org
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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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- Maple syrup urine disease
- Isovaleric acidemia
- 3-Methylcrotonyl-CoA carboxylase deficiency
- 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
- 3-Methylglutaconic aciduria 1
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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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- Sarcosinemia
- D-Glyceric acidemia
- Glutathione synthetase deficiency
- 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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- Maple syrup urine disease
- Hypervalinemia
- Isobutyryl-CoA dehydrogenase deficiency
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Isoleucine
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- Maple syrup urine disease
- Beta-ketothiolase deficiency
- 2-Methylbutyryl-CoA dehydrogenase deficiency
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Methionine
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- Hypermethioninemia
- Homocystinuria
- Cystathioninuria
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General BC/OA
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- Propionic acidemia
- Methylmalonic acidemia
- Methylmalonyl-CoA mutase deficiency
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G→fumarate
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Phenylalanine/tyrosine
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Phenylketonuria
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- Tetrahydrobiopterin deficiency
- 6-Pyruvoyltetrahydropterin synthase deficiency
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Tyrosinemia
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- Type II tyrosinemia
- Type III tyrosinemia/Hawkinsinuria
- Alkaptonuria/Ochronosis
- Type I tyrosinemia
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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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- N-Acetylglutamate synthase deficiency
- Carbamoyl phosphate synthetase I deficiency
- Ornithine transcarbamylase deficiency/translocase deficiency
- Citrullinemia
- Argininosuccinic aciduria
- Argininemia
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Transport/
IE of RTT |
- Solute carrier family: Cystinuria
- Hartnup disease
- Lysinuric protein intolerance
- Iminoglycinuria
- Fanconi syndrome: Oculocerebrorenal syndrome
- Cystinosis
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| Other |
- Trimethylaminuria
- 2-Hydroxyglutaric aciduria
- Fumarase deficiency
- Ethylmalonic encephalopathy
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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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Sex linkage: X-linked disorders
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X-linked recessive
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| Immune |
- Chronic granulomatous disease (CYBB)
- Wiskott–Aldrich syndrome
- X-linked severe combined immunodeficiency
- X-linked agammaglobulinemia
- Hyper-IgM syndrome type 1
- IPEX
- X-linked lymphoproliferative disease
- Properdin deficiency
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| Hematologic |
- Haemophilia A
- Haemophilia B
- X-linked sideroblastic anemia
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| Endocrine |
- Androgen insensitivity syndrome/Kennedy disease
- KAL1 Kallmann syndrome
- X-linked adrenal hypoplasia congenita
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| Metabolic |
- amino acid: Ornithine transcarbamylase deficiency
- Oculocerebrorenal syndrome
- dyslipidemia: Adrenoleukodystrophy
- carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
- Pyruvate dehydrogenase deficiency
- Danon disease/glycogen storage disease Type IIb
- lipid storage disorder: Fabry's disease
- mucopolysaccharidosis: Hunter syndrome
- purine-pyrimidine metabolism: Lesch–Nyhan syndrome
- mineral: Menkes disease/Occipital horn syndrome
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| Nervous system |
- X-linked mental retardation: Coffin–Lowry syndrome
- MASA syndrome
- X-linked alpha thalassemia mental retardation syndrome
- Siderius X-linked mental retardation syndrome
- eye disorders: Color blindness (red and green, but not blue)
- Ocular albinism (1)
- Norrie disease
- Choroideremia
- other: Charcot–Marie–Tooth disease (CMTX2-3)
- Pelizaeus–Merzbacher disease
- SMAX2
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| Skin and related tissue |
- Dyskeratosis congenita
- Hypohidrotic ectodermal dysplasia (EDA)
- X-linked ichthyosis
- X-linked endothelial corneal dystrophy
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| Neuromuscular |
- Becker's muscular dystrophy/Duchenne
- Centronuclear myopathy (MTM1)
- Conradi–Hünermann syndrome
- Emery–Dreifuss muscular dystrophy 1
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| Urologic |
- Alport syndrome
- Dent's disease
- X-linked nephrogenic diabetes insipidus
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| Bone/tooth |
- AMELX Amelogenesis imperfecta
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| No primary system |
- Barth syndrome
- McLeod syndrome
- Smith–Fineman–Myers syndrome
- Simpson–Golabi–Behmel syndrome
- Mohr–Tranebjærg syndrome
- Nasodigitoacoustic syndrome
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X-linked dominant
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- X-linked hypophosphatemia
- Focal dermal hypoplasia
- Fragile X syndrome
- Aicardi syndrome
- Incontinentia pigmenti
- Rett syndrome
- CHILD syndrome
- Lujan–Fryns syndrome
- Orofaciodigital syndrome 1
- Craniofrontonasal dysplasia
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