To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI) in childhood.

The clinical features, laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively. Patients with congenital adrenal hyperplasia, X-linked adrenoleukodystrophy with neurological onset or a clear family history, and autoimmune adrenal insufficiency were excluded.

The median age of 13 cases (12 males, 1 female) was 3 years and 10 months. Medical history or clinical manifestations on the first visit included hyperpigmentation, electrolyte imbalance/salt-wasting crisis, gastrointestinal symptoms, and fatigue, etc. All developments of external genitalia were normal. All cases presented with decreased serum cortisol and increased ACTH levels. Some of the cases showed decreased aldosterone level and plasma renin activity, while 17α-hydroxyprogesterone, testosterone, and androstenedione were in the normal range. Part of cases revealed delayed bone age and adrenal atrophy. Three gene mutations were detected in 13 patients, including NR0B1 gene (9/13), ABCD1 gene (3/13), and CYP11A1 gene (1/13). NR0B1, and ABCD1 gene mutations were pathogenic mutations, consistent with clinical characteristics. CYP11A1 gene mutation was heterozygote, which cannot fully explain the clinical features.

PAI in childhood presents common clinical manifestations of adrenal insufficiency, e. g. hyperpigmentation and electrolyte imbalance/salt-wasting crisis, but without specificity. Gene mutational analysis is necessary for precise diagnosis and prognosis estimation. NR0B1 and ABCD1 gene mutations were common in childhood with rare causes of PAI.

Primary adrenal insufficiency; NR0B1 gene; Mutation; Children