Interleukin 2 receptor alpha chain (IL-2Rα or CD25) deficiency (OMIM #606367) is an immune dysregulation disorder segregating in autosomal recessive form. The disease is caused by biallelic variants in the IL-2Rα gene encoding IL-2Rα also known as CD25 protein. IL-2Rα combines with γ and β chains of interleukin 2 receptor to form a functional interleukin 2 receptor (IL-2R). In the present study, we identified a Pakistani family presenting a unique presentation of IL-2Rα deficiency. Clinical whole exome sequencing revealed a novel splice donor site variant (NM_001378789.1 (NP_001365718); c.64 + 1G > A) in the IL-2Rα gene. American College of Medical Genetics (ACMG) guidelines interpreted the identified variant as likely pathogenic. The IL-2Rα gene mutation usually presents with autoimmunity and immunodeficiency but in our patient, it presents with congenital diarrhea, metabolic crisis, and strong family history of death in infancy due to the similar complications. Her congenital diarrhea is attributed to autoimmunity in the form of autoimmune enteropathy and eczema. The laboratory findings revealed severe metabolic acidosis hypokalemia and elevated lactate and ammonia levels. This is a new presentation of IL-2Rα gene mutation. The present study highlights the importance of clinical whole exome sequencing in the correct diagnosis of congenital disorders. The study will also help clinical geneticists for genetic counseling and prevention of the disease in the affected family.

白细胞介素 2 受体 α 链（IL-2Rα 或 CD25）缺乏症 (OMIM #606367) 是一种免疫失调疾病，以常染色体隐性形式分离。该疾病是由编码IL-2Rα（也称为 CD25 蛋白）的 IL-2Rα 基因的双等位基因变异引起的。IL-2Rα 与白细胞介素 2 受体的 γ 和 β 链结合形成功能性白细胞介素 2 受体 (IL-2R)。在本研究中，我们确定了一个巴基斯坦家庭呈现出独特的 IL-2Rα 缺乏症表现。临床全外显子组测序揭示了IL-2Rα基因中的新型剪接供体位点变异 (NM_001378789.1 (NP_001365718)；c.64 + 1G > A) 。美国医学遗传学学会 (ACMG) 指南将已识别的变异解释为可能致病。IL -2Rα基因突变通常表现为自身免疫和免疫缺陷，但在我们的患者中，由于类似的并发症，它表现为先天性腹泻、代谢危机和婴儿期死亡的强烈家族史。她的先天性腹泻归因于自身免疫性肠病和湿疹形式的自身免疫。实验室检查结果显示严重的代谢性酸中毒低钾血症以及乳酸和氨水平升高。这是IL-2Rα基因突变的新表现。本研究强调了临床全外显子组测序在正确诊断先天性疾病中的重要性。该研究还将帮助临床遗传学家在受影响的家庭中进行遗传咨询和疾病预防。