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(biochemistry) a nucleoside that is a structural component of nucleic acids; it is present in all living cells in a combined form as a constituent of DNA and RNA and ADP and ATP and AMP

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〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/02 19:58:44」(JST)

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Adenosine deaminase deficiency, also called ADA deficiency or ADA-SCID,^[1] is an autosomal recessive^[2] metabolic disorder that causes immunodeficiency. It occurs in fewer than one in 100,000 live births worldwide.

It accounts for about 15% of all cases of severe combined immunodeficiency (SCID).^[3] Only 3% of children are born with this gene.

ADA deficiency may be present in infancy, childhood, adolescence, or adulthood.^[1] Age of onset and severity is related to some 29 known genotypes associated with the disorder.^[4]

Pathophysiology

ADA deficiency is due to a lack of the enzyme adenosine deaminase. This deficiency results in an accumulation of deoxyadenosine,^[5] which, in turn, leads to:

a buildup of dATP in all cells, which inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide. Since developing T cells and B cells are some of the most mitotically active cells, they are highly susceptible to this condition.
an increase in S-adenosylhomocysteine since the enzyme adenosine deaminase is important in the purine salvage pathway; both substances are toxic to immature lymphocytes, which thus fail to mature.

Because T cells undergo proliferation and development in the thymus, affected individuals typically have a small, underdeveloped thymus.^[6] As a result, the immune system is severely compromised or completely lacking.

Genetics

Adenosine deaminase deficiency has an autosomal recessive pattern of inheritance.

The enzyme adenosine deaminase is encoded by a gene on chromosome 20. ADA deficiency is inherited in an autosomal recessive manner.^[1] This means the defective gene responsible for the disorder is located on an autosome (chromosome 20 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Treatment

Treatments include:

bone marrow transplant
gene therapy
ADA enzyme in PEG vehicle

On September 14, 1990, the first gene therapy to combat this disease was performed by Dr. William French Anderson on a four year old girl, Ashanti DeSilva, at the National Institutes of Health, Bethesda, Maryland, U.S.A.^[7]

References

^ ^a ^b ^c Online 'Mendelian Inheritance in Man' (OMIM) 102700
^ Hirschhorn R, Vawter GF, Kirkpatrick JA Jr., Rosen FS (September 1979). "Adenosine deaminase deficiency: frequency and comparative pathology in autosomally recessive severe combined immunodeficiency". Clinical immunology and immunopathology 14 (1): 107–20. doi:10.1016/0090-1229(79)90131-4. PMID 477037.
^ Hershfield MS (October 2003). "Genotype is an important determinant of phenotype in adenosine deaminase deficiency". Current opinion in immunology 15 (5): 571–7. doi:10.1016/S0952-7915(03)00104-3. PMID 14499267.
^ Arredondo-Vega FX, Santisteban I, Daniels S, Toutain S, Hershfield MS (October 1998). "Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles". American Journal of Human Genetics 63 (4): 1049–59. doi:10.1086/302054. PMC 1377486. PMID 9758612.
^ "Adenosine Deaminase (ADA) Deficiency". Archived from the original on 12 February 2008. Retrieved 2008-02-28.
^ p347, The Immune System Peter Parham, Garland Science, London and New York, 2009
^ Naam, Ramez (2005-07-03). "'More Than Human' - New York Times". The New York Times. Retrieved 2008-02-28.

External links

Adenosine deaminase deficiency - Genetics Home Reference

UpToDate Contents

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1. アデノシンデアミナーゼ欠損症：病因、臨床症状、および診断 adenosine deaminase deficiency pathogenesis clinical manifestations and diagnosis
2. アデノシンデアミナーゼ欠損症：治療 adenosine deaminase deficiency treatment
3. 重度複合型免疫不全（SCID）：概要 severe combined immunodeficiency scid an overview
4. 原発性免疫不全症に対する遺伝子治療 gene therapy for primary immunodeficiency
5. T-B-NK+ SCID：病因および遺伝学 t b nk scid pathogenesis and genetics

English Journal

Gene therapy for monogenic disorders of the bone marrow.

Ghosh S1,2, Thrasher AJ1, Gaspar HB1.
British journal of haematology.Br J Haematol.2015 Jun 5. doi: 10.1111/bjh.13520. [Epub ahead of print]
Ex-vivo gene transfer of autologous haematopoietic stem cells in patients with monogenic diseases of the bone marrow has emerged as a new therapeutic approach, mainly in patients lacking a suitable donor for transplant. The encouraging results of initial clinical trials of gene therapy for primary i
PMID 26044877

Outcomes in two Japanese adenosine deaminase-deficiency patients treated by stem cell gene therapy with no cytoreductive conditioning.

Otsu M1, Yamada M, Nakajima S, Kida M, Maeyama Y, Hatano N, Toita N, Takezaki S, Okura Y, Kobayashi R, Matsumoto Y, Tatsuzawa O, Tsuchida F, Kato S, Kitagawa M, Mineno J, Hershfield MS, Bali P, Candotti F, Onodera M, Kawamura N, Sakiyama Y, Ariga T.
Journal of clinical immunology.J Clin Immunol.2015 May;35(4):384-98. doi: 10.1007/s10875-015-0157-1. Epub 2015 Apr 15.
OBJECTIVE: We here describe treatment outcomes in two adenosine deaminase (ADA)-deficiency patients (pt) who received stem cell gene therapy (SCGT) with no cytoreductive conditioning. As this protocol has features distinct from those of other clinical trials, its results provide insights into SCGT f
PMID 25875699

Toll-like receptor signaling in primary immune deficiencies.

Maglione PJ1, Simchoni N, Cunningham-Rundles C.
Annals of the New York Academy of Sciences.Ann N Y Acad Sci.2015 Apr 30. doi: 10.1111/nyas.12763. [Epub ahead of print]
Toll-like receptors (TLRs) recognize common microbial or host-derived macromolecules and have important roles in early activation of the immune system. Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins to the human immune system.
PMID 25930993

Japanese Journal

原発性免疫不全症に対する遺伝子治療の現状と今後の展望

内山徹,小野寺雅史
日本臨床免疫学会会誌 36(3), 148-155, 2013
原発性免疫不全症（primary immunodeficiency, PID）の根治的治療法として造血幹細胞移植が挙げられるが，至適ドナーがいない場合には移植関連合併症の危険が増大する．このような背景から1990年代よりレトロウイルスベクターを用いた遺伝子治療がアデノシンデアミナーゼ欠損症に対し開始され，続いてX連鎖重症複合免疫不全症，ウィスコット・アルドリッチ症候群，慢性肉芽腫症など様々なP …
NAID 130003364172

Delayed onset adenosine deaminase deficiency associated with acute disseminated encephalomyelitis

NAKAOKA Hideyuki,KANEGANE Hirokazu,TANEICHI Hiromichi,MIYA Kazushi,YANG Xi,NOMURA Keiko,TAKEZAKI Shunichiro,YAMADA Masafumi,OHARA Osamu,KAMAE Chikako,IMAI Kohsuke,NONOYAMA Shigeaki,WADA Taizo,YACHIE Akihiro,HERSHFIELD Michael S.,ARIGA Tadashi,MIYAWAKI Toshio
International journal of hematology 95(6), 692-696, 2012-06-01
NAID 10030793746

先天性免疫不全症の遺伝子細胞治療

大津真
日本臨床免疫学会会誌 = Japanese journal of clinical immunology 33(6), 312-316, 2010-12-31
先天性免疫不全症候群は，生まれもった遺伝子異常のためにある種の免疫担当細胞等に欠陥が生じ，結果として免疫能の一部あるいは広範な欠損を呈する疾患群の総称である．重篤なタイプの疾患に対して造血幹細胞を標的とした遺伝子細胞治療の研究が進められており，ADA欠損症，X連鎖重症複合免疫不全症を含むいくつかの疾患において臨床試験が行われ，臨床効果が認められている．現行の治療では，ウイルスベクターを用いた治 …
NAID 10027754251

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★リンクテーブル★

リンク元	「アデノシンデアミナーゼ欠損症」
関連記事	「deficiency」「deaminase」「adenosine deaminase」

「アデノシンデアミナーゼ欠損症」

Adenosine deaminase deficiency
	Classification and external resources
ICD-10	D81.3
ICD-9	279.2
OMIM	102700
DiseasesDB	260
GeneReviews	Adenosine Deaminase Deficiency;

　　[★]

英: adenosine deaminase deficiency
同: ADA欠損症 ADA deficiency
関: アデノシンデアミナーゼ

遺伝

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参考

1. [charged] Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis - uptodate [1]
2. [charged] Adenosine deaminase deficiency: Treatment - uptodate [2]
3. ADENOSINE DEAMINASE; ADA - OMIM

http://omim.org/entry/608958