17α-羟化酶缺乏症3家系临床分析

doi:10.12372/jcp.2024.23e0665

临床儿科杂志 ›› 2024, Vol. 42 ›› Issue (5): 450-455.doi: 10.12372/jcp.2024.23e0665

17α-羟化酶缺乏症3家系临床分析

马秀琦¹, 唐怡珺², 陈瑶¹^,², 刘倩¹, 张小芳¹, 陈林¹, 张怡¹, 汪希珂¹(), 王秀敏²()

1.上海交通大学医学院附属上海儿童医学中心贵州医院贵州省人民医院儿童内分泌遗传代谢科（贵州贵阳 550003）
2.上海交通大学医学院附属上海儿童医学中心内分泌遗传代谢科（上海 200127）

收稿日期:2023-07-18 出版日期:2024-05-15 发布日期:2024-05-10
通讯作者: 王秀敏电子信箱：wangxiumin1019@126.com; 汪希珂电子信箱：wangxike2008@sina.com
基金资助:
黔科合基础-ZK(2021);国家自然科学基金(82060212)

Clinical analysis of five patients with 17α-hydroxylase deficiency from three families

MA Xiuqi¹, TANG Yijun², CHEN Yao¹^,², LIU Qian¹, ZHANG Xiaofang¹, CHEN Lin¹, ZHANG Yi¹, WANG Xike¹(), WANG Xiumin²()

1. Department of Pediatric Endocrinology, Genetics and Metabolism, Guizhou Branch of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Guizhou Provincial People's Hospital, Guiyang 550003, Guizhou, China
2. Department of Endocrinology, Genetics and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China

Received:2023-07-18 Online:2024-05-15 Published:2024-05-10

摘要/Abstract

摘要：

目的探讨并总结17α-羟化酶缺乏症的诊断及治疗。方法回顾性分析2015年11月至2023年2月儿童内分泌遗传代谢科收治的来自3个家系共5例17α-羟化酶缺乏症（17OHD）病例的临床资料，并复习相关文献。结果 5例患儿均存在高血压、低血钾及性激素水平低下，4例无第二性征发育，2例46，XY患儿行性腺活检+双侧睾丸切除术，术后性腺病理结果为发育不良的睾丸。基因分析结果提示3例为CPY17A1基因c. 985_987delinsAA纯合突变，另2例为CPY17A1基因c.785T>G与c.1193C>T复合杂合突变。5例患儿经糖皮质激素治疗，低血钾和高血压均得到控制。结论早期识别与诊断17α-羟化酶缺乏症，及时予糖皮质激素替代治疗，可获得满意的疗效，提高患儿生活质量。基因测序有助于明确该罕见病的分子学诊断。

关键词: 17α-羟化酶缺乏症, CYP17A1, 高血压, 低钾血症

Abstract:

Objective To investigate and summarize the diagnosis and treatment of 17α-hydroxylase deficiency. Methods Clinical data of a total of 5 cases of 17α-hydroxylase deficiency (17OHD) from 3 families admitted to the Department of Pediatric Endocrinology and Genetic Metabolism from November 2015 to February 2023 were retrospectively analyzed, and relevant literature was reviewed. Results Hypertension, hypokalemia and low sex hormone levels were present in all 5 cases, 4 cases had no secondary sexual development, and 2 children with 46, XY underwent gonadal biopsy and bilateral orchiectomy, and postoperative gonadal pathology showed dysplasia of testis. Genetic analysis showed that 3 cases had homozygous variants of c.985_987delinsAA, which resulted in amino acid shift line mutation (p.Tyr329Lysfs*90), and the other two cases had compound heterozygous varaiants of c.785T>G and c.1193C>T. Hypokalemia and hypertension were controlled by glucocorticoid therapy. Conclusions Early recognition and diagnosis of 17α-hydroxylase deficiency and timely glucocorticoid replacement therapy can achieve a satisfactory outcome and improve the quality of life of the children. Gene sequencing helps to clarify the molecular diagnosis of this rare disease.

Key words: 17α-hydroxylase deficiency, CYP17A1, hypertension, hypokalemia

马秀琦, 唐怡珺, 陈瑶, 刘倩, 张小芳, 陈林, 张怡, 汪希珂, 王秀敏. 17α-羟化酶缺乏症3家系临床分析[J]. 临床儿科杂志, 2024, 42(5): 450-455.

MA Xiuqi, TANG Yijun, CHEN Yao, LIU Qian, ZHANG Xiaofang, CHEN Lin, ZHANG Yi, WANG Xike, WANG Xiumin. Clinical analysis of five patients with 17α-hydroxylase deficiency from three families[J]. Journal of Clinical Pediatrics, 2024, 42(5): 450-455.

图/表 6

图1

表1

17OHD患儿5例的临床资料及基因检测结果"

项目	例1	例2	例3	例4	例5
就诊年龄/岁	11	16	12	6	11
染色体	46, XX	46, XY	46, XX	46, XY	46, XY
临床表现	高血压、低血钾、乏力、肌肉酸痛	高血压、低血钾、性发育异常、高血压性心脏病、高血压性肾病、女性外阴	高血压	高血压	高血压
血压/mmHg	210/148	191/143	150/93	136/80	140/101
性腺评估	双侧卵巢显像不清，幼稚子宫可能	腹股沟区未发现睾丸样组织	子宫体38 mm×7 mm× 14mm，右侧卵巢29 mm×13 mm× 13mm，左侧卵巢29 mm×11 mm× 13mm，双侧卵巢形态内部可见数个卵泡，较大者4mm	右侧腹股沟斜疝手术中发现睾丸样组织，病理提示小片状幼稚睾丸组织，盆腔超声未见明显子宫及卵巢组织	子宫卵巢显示不清，盆腔少量积液
骨龄	8岁10个月	13岁	12.5岁	2.5岁	5岁
肾上腺CT	双侧肾上腺增粗	右侧肾上腺结合部稍丰满	双侧肾上腺增粗	双侧肾上腺增粗	双侧肾上腺增粗，左侧显著
血钾/mmol·L^-1	2.3~2.9	2.8	3.7	3.7	4.4
醛固酮（卧位）/pg·mL^-1	64.0	67.0	84.2	85.8	284.8
皮质醇（上午8点）/μg·dL^-1	0.5	0.5	0.4	0.9	0.4
ACTH/pg·mL^-1	108.70	226.00	138.00	179.00	70.90
LH/FSH/IU·L^-1	25.7/94.5	33.3/66.5	11.7/8.8	0.2/18.4	4.7/37.6
17OHP/ng·mL^-1	0.10	0.10	0.002	0.005	0.001
E2/pg·mL^-1	30.0	<15.0	2.0	2.0	12.0
孕酮/ng·mL^-1	22.8	7.9	24.7	9.7	25.9
睾酮/ng·mL^-1	0.03	<0.10	0.45	<0.10	0.20
突变位置	Exon6	Exon6	Exon5+Exon7	Exon5+Exon7	Exon6
碱基改变	c.985_987delinsAA (homo, pat+mat)	c.985_987delinsAA (homo, pat+mat)	c.785T>G(het, pat)+ c.1193C>T(het, mat)	c.785T>G(het, pat)+ c.1193C>T(het, mat)	c.985_987delinsAA (homo, pat+mat)
氨基酸改变	p.Tyr329Lysfs*90	p.Tyr329Lysfs*90	p.Met262Arg； p.Ala398Val	p.Met262Arg； p.Ala398Val	p.Tyr329Lysfs*90
ACMG分级	PVS1+PM2+PM3 (致病性)	PVS1+PM2+PM3 (致病性)	PM2+PM3+PP3+PP4 (可能致病性) PS1+PM2+PP3+PP4 (可能致病性)	PM2+PM3+PP3+PP4 (可能致病性) PS1+PM2+PP3+PP4 (可能致病性)	PVS1+PM2+PM3 (致病性)

表1

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图5

参考文献 18

[1]	李娟, 王秀敏. 先天性肾上腺皮质增生症的诊治与管理[J]. 中华全科医师杂志, 2023, 22 (6) : 574-579.
[2]	Kim SM, Rhee JH. A case of 17 alpha-hydroxylase deficiency[J]. Clin Exp Reprod Med, 2015, 42(2): 72-76. doi: 10.5653/cerm.2015.42.2.72 pmid: 26161337
[3]	Auchus RJ. The genetics, pathophysiology, and management of human deficiencies of P450c17[J]. Endocrinol Metab Clin North Am, 2001, 30(1): 101-119. doi: 10.1016/S0889-8529(08)70021-5
[4]	Hinz L, Pacaud D, Kline G. Congenital adrenal hyperplasia causing hypertension: an illustrative review[J]. J Hum Hypertens, 2018, 32(2): 150-157. doi: 10.1038/s41371-017-0002-5 pmid: 29255217
[5]	Bee YM, Manju C, Papari-Zareei M, et al. Phenotypic variation in a Chinese family with 46,XY and 46,XX 17α-hydroxylase deficiency[J]. Gynecol Endocrinol, 2012, 28(4): 322-325. doi: 10.3109/09513590.2011.631625 pmid: 22087567
[6]	Martin RM, Lin CJ, Costa EM, et al. P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping[J]. J Clin Endocrinol Metab, 2003, 88(12): 5739-5746. doi: 10.1210/jc.2003-030988
[7]	张惠杰, 李小英. 先天性肾上腺增生症与性发育异常[J]. 中国实用内科杂志, 2011, 31(4): 254-256.
[8]	Chung BC, Picado-Leonard J, Haniu M, et al. Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues[J]. Proc Natl Acad Sci U S A, 1987, 84(2): 407-411. doi: 10.1073/pnas.84.2.407
[9]	Biglieri EG, Herron MA, Brust N. 17-hydroxylation deficiency in man[J]. J Clin Invest, 1966, 45(12): 1946-1954. doi: 10.1172/JCI105499 pmid: 4288776
[10]	胡颖, 时立新, 张淼, 等. 17-a羟化酶/17,20-裂解酶缺乏症1例诊治及相关文献复习[J]. 贵州医药, 2020, 44(3): 459-461.
[11]	Unal E, Yıldırım R, Taş FF, et al. A rare cause of delayed puberty in two cases with 46,XX and 46,XY karyotype: 17 α-hydroxylase deficiency due to a novel variant in CYP17A1 gene[J]. Gynecol Endocrinol, 2020, 36(8): 739-742. doi: 10.1080/09513590.2019.1707798
[12]	Wang M, Wang H, Zhao H, et al. Prevalence of CYP17A1 gene mutations in 17α-hydroxylase deficiency in the Chinese Han population[J]. Clin Hypertens, 2019, 25: 23. doi: 10.1186/s40885-019-0128-6
[13]	Hahm JR, Kim DR, Jeong DK, et al. A novel compound heterozygous mutation in the CYP17 (P450 17alpha-hydroxylase) gene leading to 17alpha-hydroxylase/17,20-lyase deficiency[J]. Metabolism, 2003, 52(4): 488-492. doi: 10.1053/meta.2003.50080
[14]	张一鸣, 祝捷, 叶山东. 17α-羟化酶/17,20碳链裂解酶缺陷症的研究进展及挑战[J]. 中国临床保健杂志, 2022, 25(2): 285-288.
[15]	中华医学会儿科学分会内分泌遗传代谢病学组. 先天性肾上腺皮质增生症21-羟化酶缺陷诊治共识[J]. 中华儿科杂志, 2016, 54 (8): 569-576.
[16]	刘君静, 任丽, 张卫, 等. 成年17α羟化酶缺陷症二例临床特征及诊疗分析[J]. 中国全科医学, 2021, 24(9): 1140-1143. doi: 10.12114/j.issn.1007-9572.2020.00.571
[17]	Lees B, Stevenson JC. The prevention of osteoporosis using sequential low-dose hormone replacement therapy with estradiol-17 beta and dydrogesterone[J]. Osteoporos Int, 2001, 12(4): 251-258. pmid: 11420773
[18]	蒋敏, 包明晶, 龙恩武, 等. 姐妹同患17-a羟化酶缺乏症病例分析及文献回顾[J]. 中华高血压杂志, 2022, 30(6): 593-597.

17α-羟化酶缺乏症3家系临床分析

Clinical analysis of five patients with 17α-hydroxylase deficiency from three families

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