Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Yangpu, Shanghai, China.
Department of Pediatric Endocrinology and Genetic Metabolism, Clinical Genetics Center, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Yangpu, Shanghai, China.
J Med Genet. 2023 Dec 21;61(1):27-35. doi: 10.1136/jmg-2022-108952.
Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. Differential diagnosis of numerous causes of PAI requires a thorough understanding of the condition.
To describe the genetic composition and presentations of PAI. The following data were collected retrospectively from 111 patients with non-21OHD with defined genetic diagnoses: demographic information, onset age, clinical manifestations, laboratory findings and genetic results. Patients were divided into four groups based on the underlying pathogenesis: (1) impaired steroidogenesis, (2) adrenal hypoplasia, (3) resistance to adrenocorticotropic hormone (ACTH) and (4) adrenal destruction. The age of onset was compared within the groups.
Mutations in the following genes were identified: (n=39), (n=33), (n=12), (n=8), (n=5), (n=4), (n=4), (n=2), (n=1), (n=1), (n=1) and (n=1). Frequent clinical manifestations included hyperpigmentation (73.0%), dehydration (49.5%), vomiting (37.8%) and abnormal external genitalia (23.4%). Patients with adrenal hypoplasia typically presented manifestations earlier than those with adrenal destruction but later than those with impaired steroidogenesis (both p<0.01). The elevated ACTH (92.6%) and decreased cortisol (73.5%) were the most common laboratory findings. We generated a differential diagnosis flowchart for PAI using the following clinical features: 17-hydroxyprogesterone, very-long-chain fatty acid, external genitalia, hypertension and skeletal malformation. This flowchart identified 84.8% of patients with PAI before next-generation DNA sequencing.
and were the most frequently mutated genes in patients with non-21OHD PAI. Age of onset and clinical characteristics were dependent on aetiology. Combining clinical features and molecular tests facilitates accurate diagnosis.
原发性肾上腺功能不全（PAI）是一种罕见但危及生命的疾病。为了对 PAI 的众多病因进行鉴别诊断，需要深入了解该疾病。
描述 PAI 的遗传构成和表现。我们回顾性地从 111 名具有明确遗传诊断的非 21-羟化酶缺乏症患者中收集了以下数据：人口统计学信息、发病年龄、临床表现、实验室检查结果和遗传结果。根据潜在发病机制，患者被分为四组：（1）类固醇生成障碍，（2）肾上腺发育不全，（3）促肾上腺皮质激素（ACTH）抵抗，和（4）肾上腺破坏。比较了各组之间的发病年龄。
确定了以下基因的突变：（n=39）、（n=33）、（n=12）、（n=8）、（n=5）、（n=4）、（n=4）、（n=2）、（n=1）、（n=1）、（n=1）和（n=1）。常见的临床表现包括色素沉着过度（73.0%）、脱水（49.5%）、呕吐（37.8%）和外生殖器异常（23.4%）。肾上腺发育不全的患者通常比肾上腺破坏的患者更早出现临床表现，但比类固醇生成障碍的患者更晚（均 P<0.01）。升高的 ACTH（92.6%）和降低的皮质醇（73.5%）是最常见的实验室检查结果。我们根据以下临床特征为 PAI 生成了鉴别诊断流程图：17-羟孕酮、超长链脂肪酸、外生殖器、高血压和骨骼畸形。在进行下一代 DNA 测序之前，该流程图可识别出 84.8%的 PAI 患者。
在非 21-羟化酶缺乏症 PAI 患者中，最常发生突变的基因是和。发病年龄和临床特征取决于病因。结合临床特征和分子检测有助于准确诊断。
