Abstract：
Adenosine deaminase (ADA) is a key enzyme in the purine salvage pathway. Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency. To date, few Chinese cases have been reported.
We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children\'s Hospital and summarized the previously published ADA deficiency cases from China in the literature.
Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive.
This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.
We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children\'s Hospital and summarized the previously published ADA deficiency cases from China in the literature.
Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive.
This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.
摘要：
背景：腺苷脱氨酶（ADA）是嘌呤补救途径中的关键酶。ADA基因的遗传缺陷可导致严重联合免疫缺陷的亚型。迄今为止,很少有中国病例报告。
方法：我们回顾性回顾了北京儿童医院诊断为ADA缺乏的患者的病历，并总结了以前在中国发表的ADA缺乏病例。
结果：9例患者被鉴定为两个新突变（W272X和Q202=）。早发感染,胸腺异常和无法茁壮成长是中国ADA缺乏症患者最常见的表现。ADA基因型对临床表型有主要影响。值得注意的是,一种新的同义突变(c.606G>A，p.Q202=)在延迟发作的患者中发现，这影响了前mRNA剪接，导致蛋白质的移码和过早截断。此外，患者表现出γδT细胞扩增，效果或表型增加，这可能与疾病的延迟发作有关。此外,我们首次报道了ADA缺乏的脑动脉瘤和颅内动脉狭窄。五名患者死亡，中位年龄为四个月，而两名患者接受干细胞移植并存活。
结论：本研究描述了中国人ADA缺乏患者的第一个病例系列。早发感染,胸腺异常和无法茁壮成长是我们患者最常见的表现。我们发现了一个影响ADA基因前mRNA剪接的同义突变，从未报道过ADA缺乏症。此外，我们首次报道了1例延迟发作患者的脑动脉瘤.需要进一步研究以探讨其潜在机制。
方法：我们回顾性回顾了北京儿童医院诊断为ADA缺乏的患者的病历，并总结了以前在中国发表的ADA缺乏病例。
结果：9例患者被鉴定为两个新突变（W272X和Q202=）。早发感染,胸腺异常和无法茁壮成长是中国ADA缺乏症患者最常见的表现。ADA基因型对临床表型有主要影响。值得注意的是,一种新的同义突变(c.606G>A，p.Q202=)在延迟发作的患者中发现，这影响了前mRNA剪接，导致蛋白质的移码和过早截断。此外，患者表现出γδT细胞扩增，效果或表型增加，这可能与疾病的延迟发作有关。此外,我们首次报道了ADA缺乏的脑动脉瘤和颅内动脉狭窄。五名患者死亡，中位年龄为四个月，而两名患者接受干细胞移植并存活。
结论：本研究描述了中国人ADA缺乏患者的第一个病例系列。早发感染,胸腺异常和无法茁壮成长是我们患者最常见的表现。我们发现了一个影响ADA基因前mRNA剪接的同义突变，从未报道过ADA缺乏症。此外，我们首次报道了1例延迟发作患者的脑动脉瘤.需要进一步研究以探讨其潜在机制。
