Clinical applications of genetic analysis and liquid chromatography tandem-mass spectrometry in rare types of congenital adrenal hyperplasia

BMC Endocrine Disorders

Ling Hou¹  Wei Wu¹  Caiqi Du¹  Xiao Yu¹  Yanqing Ying¹  Yan Liang¹  Xiaoping Luo¹  Zhuoguang Li² 

[1] Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Endocrinology, Shenzhen Children’s Hospital, Shenzhen, China;

关键词: Congenital adrenal hyperplasia;    Lipoid congenital adrenal hyperplasia;    11β-hydroxylase deficiency;    3β-hydroxysteroid dehydrogenase deficiency;    P450 oxidoreductase deficiency;   

DOI  :  10.1186/s12902-021-00901-8

来源: Springer

【 摘 要 】

BackgroundOur study aims to summarize the clinical characteristics of rare types of congenital adrenal hyperplasia (CAH) other than 21-hydroxylase deficiency (21-OHD), and to explore the clinical applications of genetic analysis and liquid chromatography tandem-mass spectrometry (LC-MS/MS) in rare CAH.MethodsWe retrospectively analysed the clinical data of 5 rare cases of CAH admitted to our hospital and summarized their clinical manifestations, auxiliary examinations, diagnosis and mutational spectrum.ResultsAfter gene sequencing, complex heterozygous variants were detected in all patients (2 cases were lipoid congenital adrenal hyperplasia (LCAH), 11β-hydroxylase deficiency (11β-OHD), 3β-hydroxysteroid dehydrogenase deficiency (3β-HSD deficiency) and P450 oxidoreductase deficiency (PORD) each accounted for 1 case), which were consistent with their clinical manifestations. Among them, 4 novel variants were detected, including c.650 + 2 T > A of the StAR gene, c.1145 T > C (p. L382P) of the CYP11B1 gene, c.1622C > T (p. A541V) and c.1804C > T (p. Q602 *) of the POR gene. The LC-MS/MS results for steroid hormones in patients were also consistent with their genetic variants: 2 patients with LCAH showed a decrease in all steroid hormones; 11β-OHD patient showed a significant increase in 11-deoxycortisol and 11-deoxycorticosterone; patient with 3β-HSD deficiency showed a significant increase in DHEA; and PORD patient was mainly characterized by elevated 17OHP, progesterone and impaired synthesis of androgen levels.ConclusionsThe clinical manifestations and classification of CAH are complicated, and there are cases of missed diagnosis or misdiagnosis. It’s necessary to combine the analysis of clinical manifestations and auxiliary examinations for diagnosis; if necessary, LC-MS/MS analysis of steroid hormones or gene sequencing is recommended for confirming diagnosis and typing.

【 授权许可】

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