Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
目的： 探讨类固醇生成急性调节蛋白（StAR）基因变异所致的先天性类脂性肾上腺皮质增生症（CLAH）患儿的临床和分子遗传学特点。 方法： 回顾性分析2006至2021年上海交通大学医学院附属新华医院诊断及随访的33例CLAH患儿的临床表现、实验室检查、基因检测结果及随访情况（截至2021年12月）。 结果： 33例CLAH患儿中17例染色体核型为46，XX，16例为46，XY；31例社会性别为女性，2例为男性。33例CLAH确诊年龄为9.0（3.0，34.5）月龄，其中包含30例经典型和3例非经典型，30例经典型CLAH均于新生儿或婴儿期起病，表现为皮肤色素沉着（28例，93%）、呕吐和（或）腹泻（19例，63%）、体重不增（8例，27%）等，患儿均表现为女性外生殖器。实验室检查提示血促肾上腺皮质激素均升高［21例患儿（70%）>275 pmol/L］、皮质醇降低［47（31，126）nmol/L］、低血钠［（126±13）mmol/L］、高血钾［（5.7±1.1）mmol/L］、17α-羟孕酮水平均正常。3例非经典型CLAH患儿同样有肾上腺皮质功能不全表现，其中2例（1例46，XY和1例46，XX）于1岁后起病且外生殖器分别为男性和女性，另外1例（46，XY）于2月龄起病，外生殖器为男性伴小阴茎和尿道下裂。17例46，XX女性患儿中，≥10岁的4例均有自发性青春期发育。共发现25种StAR基因变异，常见的变异为p.Q258*（27%，18/66）、p.K236Tfs*47（12%，8/66）和p.Q77*（9%，6/66），发现6种未报道的新变异（c.358T>G、c.713_714del、c.125del、c.745-1G>A、c.179-2A>C和外显子1缺失）。 结论： 经典型CLAH主要表现为婴儿早期出现原发性肾上腺皮质功能不全且外生殖器为女性外观。p.Q258*、p.K236Tfs*47和p.Q77*是CLAH患者常见的致病性变异。.