摘要目的 探讨类固醇生成急性调控蛋白(steroidogenic acute regulatory protein,StAR)基因突变致新生儿先天性类脂质性肾上腺增生症(congenital lipoid adrenal hyperplasia,CLAH)的临床特征及分子遗传学特点. 方法 回顾性分析2017年4月我院收治的1例新生儿CLAH病例的临床资料,采用高通量测序及Sanger测序对其StAR基因进行分析.在中国知网、万方数据库、PubMed等数据库中检索,收集StAR基因突变致新生儿CLAH的相关文献.将文献报道的病例进行整理分析.对纳入分析的病例要求同时具备较完整的临床资料、血清相关激素水平检测结果和StAR基因分析结果. 结果 该例患儿生后不久出现皮肤色素沉着、生长发育迟缓等肾上腺皮质功能减退症状,实验室检查发现低血钠、高血钾、促肾上腺皮质激素明显升高(263.4 pmol/L),17-羟孕酮明显降低(0.16 ng/ml)、脱氢表雄酮明显降低(＜0.95 μmol/L)、雄烯二酮明显降低(＜1.0 nmol/L)、睾酮明显降低(＜0.025 ng/ml)、孕酮降低(0.02 ng/ml)、皮质醇降低(1.6μg/ml).StAR基因分析发现,患儿存在p.Gln258X/p.Thr240fs复合杂合突变,家系分析发现患儿的2个突变分别遗传自其父亲和母亲,确诊为StAR基因突变致CLAH,经激素替代治疗后症状消失、监测电解质正常,随访至2周岁,体格生长和神经发育正常.共检索到中文文献2篇,英文文献11篇,合并本例共报道96例新生儿CLAH,其中42例有较详细资料.CLAH患儿最常见的临床表现依次为皮肤色素沉着(85.7％,36/42)、呕吐(35.7％,15/42)和生长发育迟缓(14.3％,6/42)等;有体检记录的患儿均表现为女性外生殖器(100.0％,35/35);常见的实验室检查包括低钠血症(95.2％,40/42)、高钾血症(88.1％,37/42)、促肾上腺皮质激素升高(100.0％,37/37),17-羟孕酮降低(90.5％,19/21)、皮质醇降低(86.2％,25/29)、睾酮降低(9/10)、脱氢表雄酮降低(14/14);p.Gln258X是包括中国在内的东亚患者中最常见的基因突变位点.及时开始激素替代治疗的患儿,多数预后较好. 结论 对于新生儿期出现的肾上腺皮质功能减低,尤其是生殖器呈女性外观且17-羟孕酮低的患儿,应考虑CLAH可能.染色体核型分析、基因检测等有助于诊断.及时正确的治疗,可以改善患儿预后.

abstractsObjective To investigate the clinical and molecular genetic features of neonatal congenital lipoid adrenal hyperplasia (CLAH) caused by mutations in steroidogenic acute regulatory protein (StAR) encoding gene.Methods This study retrospectively analyzed the clinical data of a CLAH neonate admitted to Fujian Provincial Matemity and Children's Hospital,Affiliated Hospital of Fujian Medical University in April 2017.StAR gene was analyzed using high-throughput sequencing and Sanger sequencing.Relevant literature retrieved from databases including China National Knowledge Infrastructure (CNKI),Wanfang and PubMed were reviewed,and the reported cases with relatively complete clinical data and results of serum hormone test and StAR gene mutation analysis were collected.Results The index patient presented with hyperpigrnentation and growth retardation soon after birth.Laboratory tests revealed hyponatremia,hyperkalemia,increased serum adrenocorticotrophic hormone (263.4 pmol/L) and decreased 17-hydroxyprogesterone (0.16 ng/ml),dehydroepiandrosterone (＜0.95 μmol/L),androstenedione (＜1.0 nmol/L),testosterone (＜0.025 ng/ml),progesterone (0.02 ng/ml) and cortisol (1.6 μ g/ml).High-throughput sequencing showed that the patient carried a compound heterozygous mutation of p.Thr240fs in exon 6 and p.Gln258X in exon 7,inherited from the father and mother,respectively.Sanger sequencing confirmed the diagnosis of CLAH caused by StAR gene mutation.After steroid replacement therapy,the patient's symptoms resolved and the concentrations of electrolytes returned to normal.The neonate was followed up to two years of age and no abnormality was found in physical or neurological development.Two Chinese and 11 English publications were retrieved and altogether 96 cases of neonatal CLAH,including the index one,were reviewed and 42 of them had detailed clinical data.The most common clinical manifestations were skin pigmentation (85.7％,36/42).Other manifestations included vomiting (35.7％,15/42) and growth retardation (14.3％,6/42).All patients with physical examination records had female external genitalia (100.0％,35/35).The common laboratory abnormalities included hyponatremia (95.2％,40/42),hyperkalemia (88.1％,37/42),elevated serum adrenocorticotrophic hormone (100.0％,37/37) and decreased 17-hydroxyprogesterone (90.5％,19/21),cortisol (86.2％,25/29),testosterone (9/10) and dehydroepiandrosterone (14/14).p.Gln258X was the most common StAR gene mutation in neonates in Eastern Asia,including China.Most cases had a good prognosis after appropriate steroid replacement.Conclusions CLAH should be considered for neonates with adrenocortical hypofunction,especially with female phenotypes and low 17-hydroxyprogesterone.Karyotyping and StAR gene analysis may be helpful in diagnosis.Timely and appropriate treatment could improve the prognosis.