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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/25 11:48:10」(JST)

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Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood.^[1] Since the substances also accumulate in the urine, the disorder can also be called citrullinuria.

Two forms of citrullinemia have been described, both having different signs and symptoms, and are caused by mutations in different genes. Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions taking place in the liver. These reactions process excess nitrogen, generated when protein is used for energy by the body, to make urea, which is excreted by the kidneys.

Types

Type I

Type I citrullinemia (Online 'Mendelian Inheritance in Man' (OMIM) 215700, also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body, they develop a lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems can be life-threatening in many cases. A milder form of type I citrullinemia is less common in childhood or adulthood. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.

Type I citrullinemia is the most common form of the disorder, affecting about one in 57,000 births worldwide. Mutations in the ASS gene cause type I citrullinemia. The enzyme made by this gene, argininosuccinate synthetase (EC 6.3.4.5), is responsible for one step of the urea cycle. Mutations in the ASS gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen, in the form of ammonia, and other byproducts of the urea cycle, accumulate in the bloodstream, leading to the characteristic features of type I citrullinemia.

Type II

The symptoms of type II citrullinemia (Online 'Mendelian Inheritance in Man' (OMIM) 605814 and Online 'Mendelian Inheritance in Man' (OMIM) 603471) usually appear during adulthood and mainly affect the central nervous system. Characteristic features include confusion, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. These symptoms can be life-threatening, and are known to be triggered by certain medications, infections, and alcohol intake in people with this type.

Type II citrullinemia may also develop in people who had a liver disorder called neonatal cholestasis during infancy. This condition blocks the flow of bile and prevents the body from processing certain nutrients properly. In many cases, the symptoms resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult type II citrullinemia.

Type II citrullinemia is primarily found in the Japanese population, where it occurs in an estimated one in 100,000 to 230,000 individuals. Type II has also been reported in people from East Asian and Middle Eastern populations. Mutations in the SLC25A13 gene are responsible for type II citrullinemia. This gene makes a protein called citrin, which normally shuttles certain molecules in and out of mitochondria. These molecules are essential for the urea cycle and are also involved in making proteins and nucleotides. Mutations in SLC25A13 typically prevent the production of any functional citrin, which inhibits the urea cycle and disrupts the production of proteins and nucleotides. The resulting buildup of ammonia and other toxic substances leads to the symptoms of type II citrullinemia. Researchers have found many infants with neonatal intrahepatic cholestasis have the same mutations in the SLC25A13 gene as adults with type II citrullinemia.

Treatment

There are multiple treatment methods. Low protein diets, are intended to minimize production of ammonia. Arginine, sodium benzoate and sodium phenylacetate help to remove ammonia from the blood. Dialysis may be used to remove ammonia from the blood when it reaches critical levels. In some cases, liver transplant has been successful.^[2]

References

^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
^ Yazaki M et al. First two cases of adult-onset type II citrullinemia successfully treated by deceased-donor liver transplantation in Japan

External links

The U.S. National Library of Medicine
GeneReviews/NCBI/NIH/UW entry on Argininosuccinate Synthetase Deficiency; ASS Deficiency; Argininosuccinic Acid Synthetase Deficiency; CTLN1; Citrullinemia, Classic
GeneReviews/NIH/UW entry on Citrin deficiency and Citrullinemia Type II

UpToDate Contents

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1. 尿素サイクル障害：管理 urea cycle disorders management
2. 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
3. 先天性代謝異常：分類 inborn errors of metabolism classification
4. 新生児胆汁うっ滞の原因 causes of neonatal cholestasis
5. 幼児および小児における小頭症：病因および評価 microcephaly in infants and children etiology and evaluation

English Journal

Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis.

Rabinovich S1, Adler L1, Yizhak K2, Sarver A1, Silberman A1, Agron S1, Stettner N1, Sun Q3, Brandis A4, Helbling D5, Korman S6, Itzkovitz S7, Dimmock D5, Ulitsky I1, Nagamani SC3,8, Ruppin E2,9,10, Erez A1.
Nature.Nature.2015 Nov 11. doi: 10.1038/nature15529. [Epub ahead of print]
Cancer cells hijack and remodel existing metabolic pathways for their benefit. Argininosuccinate synthase (ASS1) is a urea cycle enzyme that is essential in the conversion of nitrogen from ammonia and aspartate to urea. A decrease in nitrogen flux through ASS1 in the liver causes the urea cycle diso
PMID 26560030

Chronic hepatitis without hepatic steatosis caused by citrin deficiency in a child.

Inui A1, Hashimoto T1,2, Sogo T1, Komatsu H3, Saheki T4, Fujisawa T1.
Hepatology research : the official journal of the Japan Society of Hepatology.Hepatol Res.2015 Jul 18. doi: 10.1111/hepr.12559. [Epub ahead of print]
Citrin deficiency manifests as both neonatal intrahepatic cholestasis (NICCD) during early infancy and adult-onset type II citrullinemia during adulthood. Hepatic steatosis is most frequently observed in patients with citrin deficiency. Thus, non-alcoholic fatty liver disease that is unrelated to be
PMID 26190322

[Treatment and Pathomechanism of Citrin Deficiency].

Hayasaka K1, Numakura C, Watanabe H.
Brain and nerve = Shinkei kenkyū no shinpo.Brain Nerve.2015 Jun;67(6):739-47. doi: 10.11477/mf.1416200211.
Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, a small number of adults with citri
PMID 26062589

Japanese Journal

海外旅行を契機に発症した成人発症II型シトルリン血症の1例

山﨑正禎,島田拓弥,濱岡志麻 [他],柴田益成,内藤寛
臨床神経学 54(9), 747-750, 2014
症例は43歳の男性である．弟に痙攣重積で死亡の家族歴あり．3日間の海外旅行から帰った翌日から異常行動，意識障害が出現し，当科に入院した．高アンモニア血症と脳波で前頭部優位の左右差のない徐波の群発をみとめ，肝性脳症と考えた．分枝鎖アミノ酸製剤の輸液で症状は一時改善した．アミノ酸分析で血漿シトルリン高値をみとめ，遺伝子解析により成人発症II型シトルリン血症と確定診断した．食事療法と薬物療法で良好な状態 …
NAID 130004696177

SLC25A13 Gene Analysis in Citrin Deficiency: Sixteen Novel Mutations in East Asian Patients, and the Mutation Distribution in a Large Pediatric Cohort in China

Song Yuan-Zong,Zhang Zhan-Hui,Lin Wei-Xia,Zhao Xin-Jing,Deng Mei,Ma Yan-Li,Guo Li,Chen Feng-Ping,Long Xiao-Ling,He Xiang-Ling,Sunada Yoshihide,Soneda Shun,Nakatomi Akiko,Dateki Sumito,Ngu Lock-Hock,Kobayashi Keiko,Saheki Takeyori
PLoS ONE 8(9), e74544, 2013-09-19
… Background:The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). …
NAID 120005343849

Patient with adult-onset type II citrullinemia beginning 2 years after operation for duodenal malignant somatostatinoma : Indication for liver transplantation

TAZAWA Ko-ichi,YAZAKI Masahide,FUKUSHIMA Kazuhiro,OGATA Satoshi,MAKUUCHI Masatoshi,MORITA Katsuo,HIRAISHI Hideyuki,IWASAKI Yoshimi,KITA Junji,KUBOTA Keiichi,IKEDA Shu-ichi
Hepatology research : the official journal of the Japan Society of Hepatology 43(5), 563-568, 2013-05-01
NAID 10031183490

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リンク元

「シトルリン血症」

Citrullinemia
	Classification and external resources
	; L-Citrulline
ICD-10	E72.2
ICD-9	270.6
OMIM	215700 605814 603471
DiseasesDB	29676 34048
eMedicine	ped/406
MeSH	C10.228.140.163.100.175

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英: citrullinemia
関: シトルリン、argininosuccinate synthase

病因

I型：アルギニノコハク酸合成酵素遺伝子の異常。
II型：SLC25A13の遺伝子異常。

遺伝

(I型)常染色体劣性遺伝

病態

I型は新生児期に発症
II型は思春期以降に発症。

検査

血中シトルリン濃度上昇
血中アンモニア濃度上昇
その他：フェニルアラニン、メチオニン、ガラクトースが高値で見つかることがある、らしい。だから新生児マススクリーニングで見つかることがある？？？　←　出典不明！！！！！！！！！！！！

参考

1. CITRULLINEMIA, CLASSIC - OMIM

http://omim.org/entry/215700

2. [charged] Urea cycle disorders: Clinical features and diagnosis - uptodate [1]

[Fitz2-1] Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.

[2] Yazaki M et al. First two cases of adult-onset type II citrullinemia successfully treated by deceased-donor liver transplantation in Japan

匿名

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案内

案内

citrullinemia