17α-羟化酶缺乏症3家系临床分析

doi:10.12372/jcp.2024.23e0665

Abstract

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

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.

Figures/Tables 6

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)

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

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