Zheng W Q, Duan Y, Xiao B, Liang L L, Xia Y, Gong Z W, Sun Y, Zhang H W, Han L S, Wang R F, Yang Y, Zhan X, Yu Y G, Gu X F, Qiu W J
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Zhonghua Er Ke Za Zhi. 2022 Oct 2;60(10):1066-1071. doi: 10.3760/cma.j.cn112140-20220322-00233.
To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. 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. 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.K236Tfs47 (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. 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.K236Tfs47 and p.Q77 are common variants in CLAH patients.
分析33例因类固醇急性调节蛋白（StAR）基因缺陷导致的先天性类脂性肾上腺增生（CLAH）患儿的临床及遗传学特征。回顾性分析2006年至2021年在上海交通大学医学院附属新华医院确诊的33例CLAH患儿的临床、生化、遗传学及随访（截至2021年12月）资料。33例CLAH患儿中，17例核型为46,XX，16例核型为46,XY；按社会性别划分，31例为女性，2例为男性。经典型30例，非经典型3例。确诊年龄为9.0（3.0,34.5）个月。30例经典型CLAH患儿均在出生后第一年内出现皮肤色素沉着（28例，93%）、呕吐和（或）腹泻（19例，63%）、体重不增（8例，27%）、促肾上腺皮质激素水平升高（21例（70%）>275 pmol/L）、皮质醇水平降低（47（31,126）nmol/L）、低钠血症（（126±13）mmol/L）、高钾血症（（5.7±1.1）mmol/L），17α-羟孕酮水平正常（30例，100%）。所有经典型CLAH患儿均表现为女性外生殖器。3例非经典型CLAH患儿（包括2例46,XY和1例46,XX）也表现出肾上腺皮质功能减退的体征和症状，但其中2例发病年龄大于1岁，包括1例46,XY男性外生殖器和1例46,XX女性外生殖器。另1例46,XY非经典型CLAH患儿在2个月时出现肾上腺皮质功能减退，表现为小阴茎和尿道下裂。17例46,XX女性中，4例年龄大于10岁出现自发性青春期发育。33例患者共鉴定出25种StAR基因致病性变异，常见变异为p.Q258*（18/66，27%）、p.K236Tfs47（8/66，12%）和p.Q77（6/66，9%）。发现6种新变异，包括c.358T>G、c.713_714del、c.125del、c.745-1G>A、c.179-2A>C和外显子1缺失。经典型CLAH患者通常在婴儿早期出现原发性肾上腺皮质功能减退的体征和症状及女性外生殖器。p.Q258*、p.K236Tfs47和p.Q77是CLAH患者的常见变异。
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