TXNRD2基因突变致糖皮质激素缺乏1例并文献复习

A Case of Glucocorticoid Deficiency Caused by TXNRD2 Gene Mutation and Literature Review

摘要: 目的：报道1例家族性糖皮质激素缺乏(FGD)临床表现、诊治过程并进行文献复习，以提高对FGD的认识。方法：回顾性分析内蒙古自治区人民医院诊治的1例硫氧还蛋白还原2 (TXNRD2)基因突变致家族性糖皮质激素缺乏症患儿的临床资料，并检索中国知网、万方数据库、PubMed、Cochrane Library，总结TXNRD2基因突变致家族性糖皮质激素缺乏症特征及中国FGD患儿临床表现及基因类型。结果：本例患儿，男，13岁以“皮肤颜色深13年，加重3月”就诊，患儿临床表现为皮肤弥漫性黏膜色素沉着，以唇粘膜、四肢及指(趾)关节伸面及外生殖器为著，血清实验室检查示：ACTH > 1250 pg/ml，皮质醇1.62 ug/dl，17羟孕酮0.33 ng/ml，肾素–醛固酮、电解质水平正常，无失盐表现，初步诊断为原发性肾上腺皮质功能减退症；为明确病因，对患儿及其父母进行全外显子组基因测序，结果显示患儿TXNRD2基因杂合突变，22号染色体存在NM_006440.3:EX1-EX2 Del、NM_006440.3:c.949+1G>C变异，结合患儿临床表现、实验室检查及基因检测结果考虑最终明确诊断为FGD；文献复习发现FGD患儿临床表现多样，除皮肤颜色色素沉着外，还有出生后出现气促、发绀、低血糖、抽搐、间断呕吐等。结论：FGD患儿临床表现为皮肤黏膜色素沉着，血清促肾上腺皮质激素水平升高，FGD患儿存在TXNRD2基因杂合突变，国内尚无报道，提高TXNRD2基因突变致FGD的认识。

Abstract: Objective: To report the clinical manifestations, diagnosis, and treatment process of a case of Familial Glucocorticoid Deficiency (FGD) caused by a Thioredoxin Reductase 2 (TXNRD2) gene mutation, and to conduct a literature review to enhance understanding of FGD. Methods: The clinical data of a child with FGD caused by a TXNRD2 gene mutation diagnosed and treated at the Inner Mongolia Autonomous Region People’s Hospital was retrospectively analyzed. Whole-exome sequencing (WES) was performed. Literature searches were conducted in the China National Knowledge Infrastructure (CNKI), Wanfang Database, PubMed, and Cochrane Library to summarize the characteristics of FGD caused by TXNRD2 mutations and the clinical manifestations and genotypes of FGD in Chinese children. Results: Present Case: A 13-year-old male presented with the chief complaint of “darkened skin for 13 years, worsened over 3 months”. Clinical manifestations included diffuse cutaneous and mucosal hyperpigmentation, most prominent on the lips, extensor surfaces of the limbs and finger/toe joints, and external genitalia. Serum laboratory tests revealed: Adrenocorticotropic hormone (ACTH) > 1250 pg/ml (markedly elevated), cortisol 1.62 µg/dl (markedly decreased), 17-hydroxyprogesterone 0.33 ng/ml (normal). Renin-aldosterone levels and electrolytes were normal, with no signs of salt wasting. The initial diagnosis was primary adrenal insufficiency. Genetic Testing: WES of the child and his parents revealed compound heterozygous mutations in the TXNRD2 gene on chromosome 22: NM_006440.3:EX1-EX2 Del and NM_006440.3:c.949+1G>C. Based on the clinical presentation, laboratory findings, and genetic results, a definitive diagnosis of FGD caused by TXNRD2 mutations was established. Literature Review: The literature review indicated that FGD children exhibit diverse clinical manifestations. Besides characteristic cutaneous and mucosal hyperpigmentation, symptoms such as postnatal respiratory distress (tachypnea, cyanosis), hypoglycemia, seizures, and recurrent vomiting can also occur. Conclusion: FGD is clinically characterized by cutaneous and mucosal hyperpigmentation, elevated serum ACTH, and low cortisol levels. This case represents the first reported instance in China of FGD caused by compound heterozygous TXNRD2 mutations (EX1-EX2 Del and c.949+1G>C). Enhancing awareness of FGD caused by TXNRD2 gene mutations is crucial for early diagnosis and precise management.