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Abstract：
X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization.
The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed.
Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy (P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year.
This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis.
The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed.
Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy (P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year.
This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis.
摘要：
背景：X连锁先天性肾上腺发育不全（AHC）是一种罕见的疾病，其特征是原发性肾上腺功能不全（PAI）和低促性腺激素性性腺功能减退（HH），具有有限的临床和遗传特征。
方法：临床，生物化学，遗传,治疗性的,回顾性分析42例X连锁AHC患者的随访资料。
结果：色素沉着过度（38/42，90%），呕吐/腹泻(20/42，48%)，未能茁壮成长(13/42，31%)，抽搐（7/42，17％）是X连锁AHC发作时最常见的症状。促肾上腺皮质激素（ACTH）增加（42/42，100%）和皮质醇减少（37/42，88%）是最常见的实验室发现，其次是低钠血症（32/42，76％）和高钾血症（29/42，69％）。31名患者在生命的第一年内出现PAI，11岁后出现。13名14岁以上的患者中有3名表现出自发性青春期发育，其中10人因HH而经历了青春期延迟。接受人绒毛膜促性腺激素（hCG）治疗的6例患者睾丸大小略有增加，睾丸激素水平升高（均P<0.05）。3例采用脉冲促性腺激素释放激素(GnRH)治疗的患者睾丸体积均大于6例采用hCG治疗的患者(P<0.05),它们在黄体生成素（LH）方面也表现出一些增长，卵泡刺激素（FSH），和睾丸激素。在42名患者中，三个有一个Xp21缺失，和39有一个孤立的DAX1缺陷。大多数具有完整DAX1缺失的患者（9/10）占总变异体的23.8％（10/42），其早发年龄小于1岁。
结论：本研究详细介绍了X连锁AHC的临床特征和遗传谱。X连锁AHC患者的发病年龄呈双峰分布，大约70%出现在生命的第一年。当hCG治疗不令人满意时，可推荐搏动GnRH用于HH。虽然很难达到正常的睾丸体积。临床特征和分子测试的结合提供了准确诊断的信息。
方法：临床，生物化学，遗传,治疗性的,回顾性分析42例X连锁AHC患者的随访资料。
结果：色素沉着过度（38/42，90%），呕吐/腹泻(20/42，48%)，未能茁壮成长(13/42，31%)，抽搐（7/42，17％）是X连锁AHC发作时最常见的症状。促肾上腺皮质激素（ACTH）增加（42/42，100%）和皮质醇减少（37/42，88%）是最常见的实验室发现，其次是低钠血症（32/42，76％）和高钾血症（29/42，69％）。31名患者在生命的第一年内出现PAI，11岁后出现。13名14岁以上的患者中有3名表现出自发性青春期发育，其中10人因HH而经历了青春期延迟。接受人绒毛膜促性腺激素（hCG）治疗的6例患者睾丸大小略有增加，睾丸激素水平升高（均P<0.05）。3例采用脉冲促性腺激素释放激素(GnRH)治疗的患者睾丸体积均大于6例采用hCG治疗的患者(P<0.05),它们在黄体生成素（LH）方面也表现出一些增长，卵泡刺激素（FSH），和睾丸激素。在42名患者中，三个有一个Xp21缺失，和39有一个孤立的DAX1缺陷。大多数具有完整DAX1缺失的患者（9/10）占总变异体的23.8％（10/42），其早发年龄小于1岁。
结论：本研究详细介绍了X连锁AHC的临床特征和遗传谱。X连锁AHC患者的发病年龄呈双峰分布，大约70%出现在生命的第一年。当hCG治疗不令人满意时，可推荐搏动GnRH用于HH。虽然很难达到正常的睾丸体积。临床特征和分子测试的结合提供了准确诊断的信息。
