関: オルニチン回路、argininosuccinate lyase defeciency

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/13 09:31:45」(JST)

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Argininosuccinic aciduria, also called argininosuccinic acidemia, is an inherited disorder that causes the accumulation of argininosuccinic acid (also known as "ASA") in the blood and urine. Some patients may also have an elevation of ammonia, a toxic chemical, which can affect the nervous system. Argininosuccinic aciduria may become evident in the first few days of life because of high blood ammonia, or later in life presenting with "sparse" or "brittle" hair, developmental delay, and tremors.

An infant with argininosuccinic aciduria may seem lethargic or be unwilling to eat, have poorly-controlled breathing rate or body temperature, experience seizures or unusual body movements, or go into a coma. Complications from argininosuccinic aciduria may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen. Immediate treatment and lifelong management (following a strict diet and using appropriate supplements) may prevent many of these complications.

Occasionally, an individual may inherit a mild form of the disorder in which ammonia accumulates in the bloodstream only during periods of illness or other stress.

Incidence

Argininosuccinic aciduria occurs in approximately 1 in 70,000 live births. Many patients can now be detected on the newborn screen if their blood citrulline is elevated.

Genetics

Mutations in the ASL gene cause argininosuccinic aciduria. Argininosuccinic aciduria belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions in the cells of the liver. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

In argininosuccinic aciduria, the enzyme arginino succinase, that is involved in the conversion of arginino succinate to arginine within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.

Ammonia is especially damaging to the nervous system, so argininosuccinic aciduria causes neurological problems as well as eventual damage to the liver.

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

References

Kleijer WJ, Garritsen VH, Linnebank M, Mooyer P, Huijmans JG, Mustonen A, Simola KO, Arslan-Kirchner M, Battini R, Briones P, Cardo E, Mandel H, Tschiedel E, Wanders RJ, Koch HG (2002). "Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families". J Inherit Metab Dis 25 (5): 399–410. doi:10.1023/A:1020108002877. PMID 12408190.
Lee B, Goss J (2001). "Long-term correction of urea cycle disorders". J Pediatr 138 (1 Suppl): S62–71. doi:10.1067/mpd.2001.111838. PMID 11148551.
Reid Sutton V, Pan Y, Davis EC, Craigen WJ (2003). "A mouse model of argininosuccinic aciduria: biochemical characterization". Mol Genet Metab 78 (1): 11–6. doi:10.1016/S1096-7192(02)00206-8. PMID 12559843.
Scaglia F, Brunetti-Pierri N, Kleppe S, Marini J, Carter S, Garlick P, Jahoor F, O'Brien W, Lee B (2004). "Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism". J Nutr 134 (10 Suppl): 2775S–2782S; discussion 2796S–2797S. PMID 15465784. Full text
Stadler S, Gempel K, Bieger I, Pontz BF, Gerbitz KD, Bauer MF, Hofmann S (2001). "Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry". J Inherit Metab Dis 24 (3): 370–8. doi:10.1023/A:1010560704092. PMID 11486903.
Wilcken B, Smith A, Brown DA (1980). "Urine screening for aminoacidopathies: is it beneficial? Results of a long-term follow-up of cases detected bny screening one million babies". J Pediatr 97 (3): 492–7. doi:10.1016/S0022-3476(80)80216-2. PMID 7411317.

External links

ucd-overview at NIH/UW GeneTests

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. 幼児および小児における精密な神経学的評価 detailed neurologic assessment of infants and children
4. 脱毛の評価および診断 evaluation and diagnosis of hair loss

English Journal

Argininosuccinic aciduria: from a monogenic to a complex disorder.

Erez A.SourceDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. ayelet.erez@weizmann.ac.il
Genetics in medicine : official journal of the American College of Medical Genetics.Genet Med.2013 Apr;15(4):251-7. doi: 10.1038/gim.2012.166. Epub 2013 Jan 10.
In the early 1930s, phenylketonuria was among the first metabolic diseases to be defined. In the following years, multiple attempts to correlate genotype and phenotype in several inherited metabolic diseases, including phenylketonuria, were encountered with difficulties. It is becoming evident that
PMID 23306800

Ataxia.

Winchester S, Singh PK, Mikati MA.SourceDivision of Pediatric Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Handbook of clinical neurology.Handb Clin Neurol.2013;112:1213-7. doi: 10.1016/B978-0-444-52910-7.00043-X.
The approach to the child with ataxia requires a detailed history and careful general and neurological examination as well as selected blood work and brain imaging and increasingly available genetic testing for inherited ataxias that usually have an episodic or progressive presentation. The differen
PMID 23622331

A randomized controlled trial to evaluate the effects of high-dose versus low-dose of arginine therapy on hepatic function tests in argininosuccinic aciduria.

Nagamani SC, Shchelochkov OA, Mullins MA, Carter S, Lanpher BC, Sun Q, Kleppe S, Erez A, O'Brian Smith E, Marini JC; Members of the Urea Cycle Disorders Consortium, Lee B.Collaborators (20)Batshaw ML, Tuchman M, Summar ML, Baumgartner MR, Berry SA, Cederbaum S, Diaz GA, Gallagher RC, Harding CO, Hoffmann G, Kerr DS, Lichter-Konecki U, McCandless SE, Merritt J, Schulze A, Seashore MR, Stricker T, Waisbren S, Wong D, Yudkoff M.
Molecular genetics and metabolism.Mol Genet Metab.2012 Nov;107(3):315-21. doi: 10.1016/j.ymgme.2012.09.016. Epub 2012 Sep 17.
OBJECTIVE: To compare the effects of combinatorial therapy with low-dose arginine and a nitrogen scavenging agent (sodium phenylbutyrate) vs. monotherapy with high-dose arginine on liver function tests in patients with argininosuccinic aciduria (ASA).STUDY DESIGN: Twelve patients with ASA were enrol
PMID 23040521