Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pediatric Genetic and Metabolic Endocrinology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Endocrinol (Lausanne). 2022 Nov 2;13:947762. doi: 10.3389/fendo.2022.947762. eCollection 2022.
Lipoid congenital adrenal hyperplasia (LCAH) is a rare and severe disorder that is caused by mutations in the steroidogenic acute regulatory protein (StAR). Non-classic LCAH is defined as late-onset glucocorticoid deficiency and even complete male external genitalia in 46,XY individuals. However, to date, few cases of non-classic LCAH have been reported.
It was attempted to describe the clinical characteristics of a male child with complete male external genitalia in terms of age of onset, adrenal function, and biochemical indicators. Previously reported cases were also reviewed to investigate the relationship of age of onset with enzymatic activity in non-classic LCAH.
The patient with complete male external genitalia was diagnosed with non-classic LCAH, in which the reason for his referral to a local hospital at the of age 1.25 years was progressive skin hyperpigmentation, and plasma adrenocorticotropic hormone (ACTH) level was elevated to higher than 1,250 pg/ml. The compound heterozygous mutations c.772C>T/c.562C>T in gene were identified genetic testing. The literature review resulted in identification of 47 patients with non-classic LCAH from 36 families. The mutational analysis showed that c.562C>T mutation was prevalent in patients with non-classic LCAH, accounting for 37.2% of the total mutant alleles, which could reflect the founder effect on the non-classic LCAH population. In total, 28 46,XY patients were reported, including 22 (78.5%) cases with complete male external genitalia and six (21.5%) cases with different degrees of hypospadias.
The clinical phenotypes of non-classic LCAH are highly variable. Routine physical examination, laboratory measurement, genetic testing, and, importantly, enzymatic activity assay may facilitate the early diagnosis of non-classic LCAH. The age of primary adrenal insufficiency (PAI) onset may not be a diagnostic basis for non-classic LCAH, and enzymatic activity assay determination may be more effective.
脂质型先天性肾上腺皮质增生症（LCAH）是一种罕见且严重的疾病，由类固醇急性调节蛋白（StAR）基因突变引起。非经典型 LCAH 的定义为迟发性糖皮质激素缺乏症，甚至在 46,XY 个体中出现完全男性外生殖器。然而，迄今为止，非经典型 LCAH 的病例报道较少。
尝试根据发病年龄、肾上腺功能和生化指标描述一名具有完全男性外生殖器的男性儿童的临床特征。还回顾了以前的病例报告，以研究非经典型 LCAH 发病年龄与酶活性的关系。
该具有完全男性外生殖器的患者被诊断为非经典型 LCAH，其 1.25 岁时因进行性皮肤色素沉着加深而被当地医院转介。血浆促肾上腺皮质激素（ACTH）水平升高至高于 1,250pg/ml。基因检测发现基因中的复合杂合突变 c.772C>T/c.562C>T。文献回顾共从 36 个家系中确定了 47 例非经典型 LCAH 患者。突变分析显示，c.562C>T 突变在非经典型 LCAH 患者中较为常见，占总突变等位基因的 37.2%，这可能反映了非经典型 LCAH 人群中的起源效应。共有 28 例 46,XY 患者报道，其中 22 例（78.5%）患者具有完全男性外生殖器，6 例（21.5%）患者具有不同程度的尿道下裂。
非经典型 LCAH 的临床表型高度可变。常规体格检查、实验室测量、基因检测，特别是酶活性测定，有助于早期诊断非经典型 LCAH。原发性肾上腺功能不全（PAI）发病年龄可能不是非经典型 LCAH 的诊断依据，酶活性测定可能更为有效。
