Activated phosphoinositide 3-kinase δ syndrome associated with nephromegaly, growth hormone deficiency, bronchiectasis: a case report.
Activated phosphoinositide 3-kinase δ syndrome associated with nephromegaly, growth hormone deficiency, bronchiectasis: a case report.
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DOI：
10.1186/s13223-022-00655-5
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发表时间：
2022-02-21
期刊：
影响因子：
--
通讯作者：
Cernelc-Kohan M
中科院分区：
文献类型：
--
作者：
Craig M;Geng B;Wigby K;Phillips SA;Bakhoum C;Naheedy J;Cernelc-Kohan M
活化型磷脂酰肌醇3-激酶（PI 3 K）δ综合征（APDS）是一种罕见的原发性免疫缺陷症，文献报道了243例已知病例。已知与该疾病相关的发现包括复发性鼻窦炎和支气管炎、支气管扩张、免疫性血细胞减少、轻度发育迟缓、脾肿大和淋巴结病。我们报告的情况下，儿童APDS伴随着独特的临床特征：肾肥大和生长激素缺乏症相关的垂体解剖异常。患者是一名9岁男孩，患有磷脂酰肌醇-4，5-二磷酸3-激酶催化亚基δ（p.E1021K）的杂合性新生变异，既往报告与APDS相关。我们的病人，谁没有免疫缺陷家族史，表现出这种综合征的经典结果，但也有独特的功能，扩大了这种疾病的表型谱。在5岁时，患者表现出明显的生长减速，并被证明有生长激素（GH）缺乏症与相关的垂体解剖异常。他开始了GH治疗，反应非常好。他还患有病因不明的双侧肾肥大、镜下血尿和蛋白尿、哮喘，并出现左髋疼痛伴关节穿刺术，与少关节幼年特发性关节炎一致。在9岁时，患者被转介到遗传学和全外显子组测序显示APDS。尽管最初担心GH可能会增加恶性肿瘤的风险，因为GH通过PI 3 K途径发出信号，但允许患者继续治疗，因为认为PI 3 K途径在基线时具有组成性活性。我们的病人的独特介绍增加了有关APDS的临床信息，证明了基因检测的实用性，并说明了多学科协作方法在管理这种复杂综合征中的重要性。在线版本包含补充材料，可通过10.1186/s13223-022-00655-5获得。
Activated phosphoinositide 3-kinase (PI3K) δ syndrome (APDS) is a rare form of primary immunodeficiency with 243 known cases reported in the literature. Known findings associated with the condition include recurrent sinusitis and bronchitis, bronchiectasis, immune cytopenias, mild developmental delay, splenomegaly, and lymphadenopathy. We report the case of a child with APDS accompanied by unique clinical features: nephromegaly and growth hormone deficiency with associated pituitary anatomic abnormality. The patient is a nine-year-old boy with a heterozygous de novo variant in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit δ (p.E1021K), previously reported in association with APDS. Our patient, who had no family history of immunodeficiency, exhibits classic findings of this syndrome but also has unique features that extend the phenotypic spectrum of this disorder. At 5 years of age, the patient showed marked growth deceleration and was demonstrated to have growth hormone (GH) deficiency with associated pituitary anatomic abnormality. He started GH therapy with an excellent response. He additionally has bilateral nephromegaly of unclear etiology, microscopic hematuria and proteinuria, asthma, and has developed left hip pain with arthrocentesis consistent with oligoarticular juvenile idiopathic arthritis. At age nine, the patient was referred to genetics and whole exome sequencing revealed APDS. Though there was initial concern that GH may increase risk for malignancy as GH signals through the PI3K pathway, he was allowed to continue treatment as the PI3K pathway was considered constitutively active at baseline. Our patient’s unique presentation adds to the clinical information regarding APDS, demonstrates the utility of genetic testing and illustrates the importance of a multidisciplinary collaborative approach in managing this complex syndrome. The online version contains supplementary material available at 10.1186/s13223-022-00655-5.
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