以严重高血压就诊的17α-羟化酶缺乏症
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摘要
患儿,女(社会性别),14岁,因发现高血压11 d入院。患儿无月经来潮。查体:血压146/90 mm Hg,肤色略黑,乳腺未发育,可见大阴唇,未见小阴唇、阴蒂、阴道及处女膜。实验室检测发现低肾素、低皮质醇、高促肾上腺皮质激素,低性激素、高促性腺激素,血钾、醛固酮未见异常;影像学提示骨龄落后,无卵巢、子宫,双侧肾上腺皮质增生,双侧腹股沟区隐睾。染色体核型46,XY。全基因组测序提示:CYP17A1外显子区域2个纯合突变,c.985T>C(胸腺嘧啶突变为腺嘌呤)和c.987del C(缺失突变),父母存在上述2个位点的杂合突变。确诊为先天性肾上腺皮质增生症17α-羟化酶缺乏症。给予氢化可的松治疗2个月后血压恢复正常,ACTH下降,继续氢化可的松治疗,并应患儿及父母要求按女性治疗,加用雌激素替代,手术切除隐睾。儿童高血压的鉴别诊断也应注意儿童性发育情况,筛查ACTH和皮质醇,以免误诊;对低肾素性高血压伴性发育落后者应注意鉴别罕见病17α-羟化酶缺乏症。
A 14-year-old female(social gender) patient was admitted to the hospital due to severe hypertension for 11 days. The patient had primary amenorrhea. The blood pressure was 146/90 mmHg. The skin color was slightly black. The development of secondary sexual characteristics was poor. The labia majora could be observed in the vulva. However, the labia minora, clitoris, vagina, and hymen were absent. The levels of renin, cortisol, and sex hormone were low, while the levels of adrenocorticotropic hormone and gonadotropin were high. The levels of blood potassium and aldosterone were both normal. Radiography indicated retardation of bone age. Ultrasound examination revealed that the ovary and uterus were both absent. The patient had bilateral adrenal hyperplasia and cryptorchid testes located in both inguinal canals. The patient had a 46,XY karyotype. Whole genome sequencing revealed two homozygous mutations, c.985 T>C and c.987 del C, in exon 6 of the CYP17A1 gene of the patient and heterozygous mutations in the same sites of the parents. The patient was diagnosed with congenital adrenal hyperplasia-17α-hydroxylase deficiency. After treatment with hydrocortisone for 2 months, blood pressure returned to normal and the level of adrenocorticotropic hormone was reduced. According to the request of the patient and the parents, hydrocortisone was replaced with estrogen to allow the patient to live as a female. The patient also received surgical excision of cryptorchid testes to prevent gonadal malignancy. It is concluded that in the differential diagnosis of pediatric hypertension, sexual development should be considered and the levels of adrenocorticotropic hormone and cortisol should be evaluated. The rare disease 17α-hydroxylase deficiency should be considered for patients with low-renin hypertension and gonadal dysgenesis.
A 14-year-old female(social gender) patient was admitted to the hospital due to severe hypertension for 11 days. The patient had primary amenorrhea. The blood pressure was 146/90 mmHg. The skin color was slightly black. The development of secondary sexual characteristics was poor. The labia majora could be observed in the vulva. However, the labia minora, clitoris, vagina, and hymen were absent. The levels of renin, cortisol, and sex hormone were low, while the levels of adrenocorticotropic hormone and gonadotropin were high. The levels of blood potassium and aldosterone were both normal. Radiography indicated retardation of bone age. Ultrasound examination revealed that the ovary and uterus were both absent. The patient had bilateral adrenal hyperplasia and cryptorchid testes located in both inguinal canals. The patient had a 46,XY karyotype. Whole genome sequencing revealed two homozygous mutations, c.985 T>C and c.987 del C, in exon 6 of the CYP17A1 gene of the patient and heterozygous mutations in the same sites of the parents. The patient was diagnosed with congenital adrenal hyperplasia-17α-hydroxylase deficiency. After treatment with hydrocortisone for 2 months, blood pressure returned to normal and the level of adrenocorticotropic hormone was reduced. According to the request of the patient and the parents, hydrocortisone was replaced with estrogen to allow the patient to live as a female. The patient also received surgical excision of cryptorchid testes to prevent gonadal malignancy. It is concluded that in the differential diagnosis of pediatric hypertension, sexual development should be considered and the levels of adrenocorticotropic hormone and cortisol should be evaluated. The rare disease 17α-hydroxylase deficiency should be considered for patients with low-renin hypertension and gonadal dysgenesis.
引文
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[4]周莹,黄爱洁,符金香,等.17α-羟化酶/17,20-碳链裂解酶缺陷症不典型病例1例报告[J].中国实用内科杂志,2016,36(8):716-717.
[5]刘杰,黄沁松.17α-羟化酶缺乏症男性假两性畸形1例报告[J].中国实用妇科与产科杂志,2017,33(12):1311-1312.
[6]Wu C,Fan S,Qian Y,et al.17α-hydroxylase/17,20-lyase deficiency:clinical and molecular characterization of eight Chinese patients[J].Endocr Pract,2017,23(5):576-582.
[7]Auchus RJ.Steroid 17-hydroxylase and 17,20-lyase deficiencies,genetic and pharmacologic[J].J Steroid Biochem Mol Biol,2017,165(Pt A):71-78.
[8]Miller WL.The syndrome of 17,20 lyase deficiency[J].J Clin Endocrinol Metab,2012,97(1):59-67.
[9]Deeb A,Al Suwaidi H,Attia S,et al.17-hydroxylase/17,20-lyase deficiency due to a R96Q mutation causing hypertension and poor breast development[J].Endocrinol Diabetes Metab Case Rep,2015:150069.
[10]Soveid M,Rais-Jalali GA.Seventeen alpha-hydroxylase deficiency associated with absent gonads and myelolipoma:A case report and review of literature[J].Iran J Med Sci,2016,41(6):543-547.
[11]Kü?ükemre-Ayd?n B,??rendil-Yanar ?,Bilge I,et al.An easily missed diagnosis:17-alpha-hydroxylase/17,20-lyase deficiency[J].Turk J Pediatr,2015,57(3):277-281.
[12]Kim YM,Kang M,Choi JH,et al.A review of the literature on common CYP17A1 mutations in adults with17-hydroxylase/17,20-lyase deficiency,a case series of such mutations among Koreans and functional characteristics of a novel mutation[J].Metabolism,2014,63(1):42-49.
[13]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.
[14]Xu S,Hu S,Yu X,et al.17αhydroxylase/17,20 lyase deficiency in congenital adrenal hyperplasia:A case report[J].Mol Med Rep,2017,15(1):339-344.
[15]Fernández-Cancio M,García-García E,González-Cejudo C,et al.Discordant genotypic sex and phenotype variations in two spanish siblings with 17α-Hydroxylase/17,20-Lyase deficiency carrying the most prevalent mutated CYP17A1 alleles of Brazilian patients[J].Sex Dev,2017,11(2):70-77.
[16]Turan S,Bereket A,Guran T,et al.Puberty in a case with novel17-hydroxylase mutation and the putative role of estrogen in development of pubic hair[J].Eur J Endocrinol,2009,160(2):325-330.
[17]Kim SM,Rhee JH.A case of 17 alpha-hydroxylase deficiency[J].Clin Exp Reprod Med,2015,42(2):72-76.
[18]Jiang JF,Xue W,Deng Y,et al.Gonadal malignancy in 202female patients with disorders of sex development containing Y-chromosome material[J].Gynecol Endocrinol,2016,32(4):338-341.
[2]Hinz L,Pacaud D,Kline G.Congenital adrenal hyperplasia causing hypertension:an illustrative review[J].J Hum Hypertens,2017,32(2):150-157.
[3]Fleming L,Van Riper M,Knafl K.Management of childhood congenital adrenal hyperplasia-An integrative review of the literature[J].J Pediatr Health Care,2017,31(5):560-577.
[4]周莹,黄爱洁,符金香,等.17α-羟化酶/17,20-碳链裂解酶缺陷症不典型病例1例报告[J].中国实用内科杂志,2016,36(8):716-717.
[5]刘杰,黄沁松.17α-羟化酶缺乏症男性假两性畸形1例报告[J].中国实用妇科与产科杂志,2017,33(12):1311-1312.
[6]Wu C,Fan S,Qian Y,et al.17α-hydroxylase/17,20-lyase deficiency:clinical and molecular characterization of eight Chinese patients[J].Endocr Pract,2017,23(5):576-582.
[7]Auchus RJ.Steroid 17-hydroxylase and 17,20-lyase deficiencies,genetic and pharmacologic[J].J Steroid Biochem Mol Biol,2017,165(Pt A):71-78.
[8]Miller WL.The syndrome of 17,20 lyase deficiency[J].J Clin Endocrinol Metab,2012,97(1):59-67.
[9]Deeb A,Al Suwaidi H,Attia S,et al.17-hydroxylase/17,20-lyase deficiency due to a R96Q mutation causing hypertension and poor breast development[J].Endocrinol Diabetes Metab Case Rep,2015:150069.
[10]Soveid M,Rais-Jalali GA.Seventeen alpha-hydroxylase deficiency associated with absent gonads and myelolipoma:A case report and review of literature[J].Iran J Med Sci,2016,41(6):543-547.
[11]Kü?ükemre-Ayd?n B,??rendil-Yanar ?,Bilge I,et al.An easily missed diagnosis:17-alpha-hydroxylase/17,20-lyase deficiency[J].Turk J Pediatr,2015,57(3):277-281.
[12]Kim YM,Kang M,Choi JH,et al.A review of the literature on common CYP17A1 mutations in adults with17-hydroxylase/17,20-lyase deficiency,a case series of such mutations among Koreans and functional characteristics of a novel mutation[J].Metabolism,2014,63(1):42-49.
[13]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.
[14]Xu S,Hu S,Yu X,et al.17αhydroxylase/17,20 lyase deficiency in congenital adrenal hyperplasia:A case report[J].Mol Med Rep,2017,15(1):339-344.
[15]Fernández-Cancio M,García-García E,González-Cejudo C,et al.Discordant genotypic sex and phenotype variations in two spanish siblings with 17α-Hydroxylase/17,20-Lyase deficiency carrying the most prevalent mutated CYP17A1 alleles of Brazilian patients[J].Sex Dev,2017,11(2):70-77.
[16]Turan S,Bereket A,Guran T,et al.Puberty in a case with novel17-hydroxylase mutation and the putative role of estrogen in development of pubic hair[J].Eur J Endocrinol,2009,160(2):325-330.
[17]Kim SM,Rhee JH.A case of 17 alpha-hydroxylase deficiency[J].Clin Exp Reprod Med,2015,42(2):72-76.
[18]Jiang JF,Xue W,Deng Y,et al.Gonadal malignancy in 202female patients with disorders of sex development containing Y-chromosome material[J].Gynecol Endocrinol,2016,32(4):338-341.