Adenosine deaminase deficiency in adults
Adenosine deaminase deficiency in adults
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DOI：
10.1182/blood.v89.8.2849
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发表时间：
1997-04-15
期刊：
影响因子：
20.3
通讯作者：
Hershfield, MS
中科院分区：
文献类型：
--
作者：
Ozsahin, H;ArredondoVega, FX;Hershfield, MS
腺苷脱氨酶 (ADA) 缺乏通常会导致婴儿严重联合免疫缺陷 (SCID)。我们报告了两名具有不同表型的 ADA 缺陷成年人的代谢、免疫学和遗传学发现。患者编号1 名（39 岁）患有联合免疫缺陷。她小时候经常感染、淋巴细胞减少和肝炎复发，但在她的第二个和第三个十年里，情况相对较好。随后，她出现了慢性鼻窦肺部感染，包括肺结核和肝胆疾病；她于 40 岁时死于病毒性白质脑病。患者编号2号是一名健康的28岁男性，免疫功能正常，在他的侄女死于SCID后被确诊。两名患者均缺乏红细胞 ADA 活性，但脱氧腺苷核苷酸仅轻度升高。两者都是错义突变的异等位基因：患者编号。 1、G216R和P126Q（新型）；患者编号2、R101Q和A215T。其中三个突变消除了 ADA 活性，但 A215T 仅降低了 85% 的活性。由于外显子 7 中部的单个核苷酸变化，A215T 似乎也诱导外显子 7 跳跃。 ADA 缺乏症是可以治疗的，对于患有不明原因淋巴细胞减少和免疫缺陷的老年患者应予以考虑，这些患者还可能表现出自身免疫或不明原因肝胆疾病。代谢状态和基因型可能有助于评估较轻度受影响患者的预后。 (C) 1997 年，美国血液学会。
Adenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenotypes. Patient no. 1 (39 years of age) had combined immunodeficiency. She had frequent infections, lymphopenia, and recurrent hepatitis as a child but did relatively well in her second and third decades. Then she developed chronic sinopulmonary infections, including tuberculosis, and hepatobiliary disease; she died of viral leukoencephalopathy at 40 years of age. Patient no. 2, a healthy 28-year-old man with normal immune function, was identified after his niece died of SCID. Both patients lacked erythrocyte ADA activity but had only modestly elevated deoxyadenosine nucleotides. Both were heteroallelic for missense mutations: patient no. 1, G216R and P126Q (novel); patient no. 2, R101Q and A215T. Three of these mutations eliminated ADA activity, but A215T reduced activity by only 85%. Owing to a single nucleotide change in the middle of exon 7, A215T also appeared to induce exon 7 skipping. ADA deficiency is treatable and should be considered in older patients with unexplained lymphopenia and immune deficiency, who may also manifest autoimmunity or unexplained hepatobiliary disease. Metabolic status and genotype may help in assessing prognosis of more mildly affected patients. (C) 1997 by The American Society of Hematology.