関: argininemia

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/15 14:01:50」(JST)

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Argininemia, also called arginase deficiency,^[1] is an autosomal recessive^[2] urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood.

Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Diagnosis

Argininemia usually becomes evident by about the age of 3. It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity). Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, mental retardation, seizures, tremor, and difficulty with balance and coordination (ataxia). Occasionally, high protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting.

In some affected individuals, signs and symptoms of argininemia may be less severe, and may not appear until later in life.

Genetics

Argininemia has an autosomal recessive pattern of inheritance.

Mutations in the ARG1 gene cause argininemia.

Argininemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, making a compound called urea that is excreted by the kidneys.

The ARG1 gene provides instructions for making an enzyme called arginase. This enzyme controls the final step of the urea cycle, which produces urea by removing nitrogen from arginine. In people with arginase deficiency, arginase is damaged or missing, and arginine is not broken down properly. As a result, urea cannot be produced normally, and excess nitrogen accumulates in the blood in the form of ammonia. The accumulation of ammonia and arginine are believed to cause the neurological problems and other signs and symptoms of arginase deficiency. The accumulation of guanidino metabolites also contribute to the neurotoxicity of the disease.^[3]

This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome, and two copies of the defective gene are required to inherit the disorder. Both parents of an individual with an autosomal recessive disorder are carriers of one copy of the gene, but usually do not have the disorder.

References

^ Online 'Mendelian Inheritance in Man' (OMIM) 207800
^ Uchino, Takako; Snyderman, Selma E.; Lambert, Marie; Qureshi, Ijaz A.; Shapira, Stuart K.; Sansaricq, Claude; Smit, Leonard M. E.; Jakobs, Cornelis; Matsuda, Ichiro (1995). "Molecular basis of phenotypic variation in patients with argininemia". Human Genetics 96 (3): 255–60. doi:10.1007/BF00210403. PMID 7649538.
^ Deignan, Joshua L.; Marescau, Bart; Livesay, Justin C.; Iyer, Ramaswamy K.; De Deyn, Peter P.; Cederbaum, Stephen D.; Grody, Wayne W. (2008). "Increased plasma and tissue guanidino compounds in a mouse model of hyperargininemia". Molecular Genetics and Metabolism 93 (2): 172–8. doi:10.1016/j.ymgme.2007.09.016. PMID 17997338.

External links

GeneReviews/NCBI/NIH/UW entry on Urea Cycle Disorders Overview
GeneReviews/NCBI/NIH/UW entry on Arginase Deficiency or Hyperargininemia
OMIM entries on Arginase Deficiency
Argininemia at NLM Genetics Home Reference

UpToDate Contents

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1. 尿素サイクル障害：臨床的特徴および診断 urea cycle disorders clinical features and diagnosis
2. 尿素サイクル障害：管理 urea cycle disorders management
3. 先天性代謝異常：疫学、病因、および臨床的特徴 inborn errors of metabolism epidemiology pathogenesis and clinical features
4. 遺伝性痙性対麻痺 hereditary spastic paraplegia
5. Evaluation and diagnosis of cerebral palsy

English Journal

Effect of N-acetylarginine, a metabolite accumulated in hyperargininemia, on parameters of oxidative stress in rats: protective role of vitamins and L-NAME.

Sasso S1, Dalmedico L, Delwing-Dal Magro D, Wyse AT, Delwing-de Lima D.
Cell biochemistry and function.Cell Biochem Funct.2014 Jul 15. doi: 10.1002/cbf.3045. [Epub ahead of print]
In the present investigation, we initially evaluated the in vitro effect of N-acetylarginine on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-P
PMID 25042906

Hyperargininemia: 7-Month Follow-Up Under Sodium Benzoate Therapy in an Italian Child Presenting Progressive Spastic Paraparesis, Cognitive Decline, and Novel Mutation in ARG1 Gene.

Baranello G1, Alfei E2, Martinelli D3, Rizzetto M4, Cazzaniga F2, Dionisi-Vici C3, Gellera C4, Castellotti B4.
Pediatric neurology.Pediatr Neurol.2014 Jun 4. pii: S0887-8994(14)00333-6. doi: 10.1016/j.pediatrneurol.2014.05.029. [Epub ahead of print]
BACKGROUND: Hyperargininemia due to mutations in ARG1 gene is an autosomal recessive inborn error of metabolism caused by a defect in the final step of the urea cycle. Common clinical presentation is a variable association of progressive spastic paraparesis, epilepsy, and cognitive deficits.METHODS:
PMID 24997092

Myocyte-mediated Arginase Expression Controls Hyperargininemia but not Hyperammonemia in Arginase-deficient Mice.

Hu C1, Kasten J1, Park H1, Bhargava R1, Tai DS1, Grody WW2, Nguyen QG3, Hauschka SD3, Cederbaum SD4, Lipshutz GS5.
Molecular therapy : the journal of the American Society of Gene Therapy.Mol Ther.2014 Jun 3. doi: 10.1038/mt.2014.99. [Epub ahead of print]
Human arginase deficiency is characterized by hyperargininemia and infrequent episodes of hyperammonemia that cause neurological impairment and growth retardation. We previously developed a neonatal mouse adeno-associated viral vector (AAV) rh10-mediated therapeutic approach with arginase expressed
PMID 24888478

Japanese Journal

54. わが国における人および猿のアルギナーゼ欠損症

藤本昭栄,大浦敏明,大沢済
先天異常 : 日本先天異常学会会報 : official journal of Congeital Anomalies Research Association of Japan 19(3), 190, 1979-09-30
NAID 110002727011

実験的高アルギニン血症ウサギに関する研究第1編アルギニン大量負荷ウサギの血清,尿および脳組織中のアミノ酸並びにグアニジノ化合物について

洲脇貞吉
岡山医学会雑誌 90(9-10), 1093-1104, 1978-10-30
… A hyperargininemia was induced by oraly administration of arginine in rabbit, and amino acids and guanidino compounds were analysed in the serum, urine and brain. …
NAID 120002308898