PT  - JOURNAL ARTICLE
AU  - Duan, Ying
AU  - Zheng, Wanqi
AU  - Xia, Yu
AU  - Zhang, Huiwen
AU  - Liang, Lili
AU  - Wang, Ruifang
AU  - Yang, Yi
AU  - Zhang, Kaichuang
AU  - Lu, Deyun
AU  - Sun, Yuning
AU  - Han, Lianshu
AU  - Yu, Yongguo
AU  - Gu, Xuefan
AU  - Sun, Yu
AU  - Xiao, Bing
AU  - Qiu, Wenjuan
TI  - Genetic and phenotypic spectrum of non-21-hydroxylase-deficiency primary adrenal insufficiency in childhood: data from 111 Chinese patients
AID  - 10.1136/jmg-2022-108952
DP  - 2024 Jan 01
TA  - Journal of Medical Genetics
PG  - 27--35
VI  - 61
IP  - 1
4099  - http://jmg.bmj.com/content/61/1/27.short
4100  - http://jmg.bmj.com/content/61/1/27.full
SO  - J Med Genet2024 Jan 01; 61
AB  - Background 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.Methods 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.Results Mutations in the following genes were identified: NR0B1 (n=39), STAR (n=33), CYP11B1 (n=12), ABCD1 (n=8), CYP17A1 (n=5), HSD3B2 (n=4), POR (n=4), MRAP (n=2), MC2R (n=1), CYP11A1 (n=1), LIPA (n=1) and SAMD9 (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.Conclusions STAR and NR0B1 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.Data are available upon reasonable request. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.