Tankoska Maja, Anastasovska Violeta, Krstevska-Konstantinova Marina, Naydenov Michel, Kocova Mirjana
Student at Medical Faculty, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia.
Genetic Laboratory, Department of Endocrinology and Genetics, University Pediatric Clinic, Medical Faculty, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia.
J Pediatr Endocrinol Metab. 2019 May 27;32(5):543-547. doi: 10.1515/jpem-2018-0285.
Background Steroid 21-hydroxylase deficiency is an autosomal recessive disorder, present in 90-95% of all cases with congenital adrenal hyperplasia (CAH). The classical simple virilizing (SV) form of the disease causes virilization of the external genitalia in newborn females and pseudo-precocious puberty in both sexes, due to reactive androgen overproduction. Case presentation We describe a 3.5-year-old girl presenting with pubarche, P2 according to Tanner, advanced bone age of 6 years and 10 months, and high serum levels of 17-hydroxyprogesterone (17-OHP). Molecular analysis of the nine most common pseudogene-derived CYP21A2 point mutations was performed in the patient and her family members using the polymerase chain reaction/amplification-created restriction site (PCR/ACRS) method. We detected the P30L/I172N genotype in the patient. She had inherited a mild P30L mutation from her mother and a severe I172N mutation from her father. Conclusions Although the CAH phenotype is determined by the allele that produces most of the enzyme activity and the mild non-classical (NC) phenotype should be expected, the mild P30L known to be more virilizing probably induced the classical SV phenotype in our patient. A continuous regimen of hydrocortisone at a recommended dose failed to decrease the 17-OHP sufficiently. Careful tapering of the dose did not help, and her pubic hair advanced to P3 according to Tanner. Individually tailored treatment is warranted in this patient.
类固醇21-羟化酶缺乏症是一种常染色体隐性疾病，在所有先天性肾上腺皮质增生症（CAH）病例中占90 - 95%。该疾病的经典单纯男性化（SV）形式会导致新生女婴外生殖器男性化以及男女两性的假性性早熟，这是由于反应性雄激素过度产生所致。病例报告：我们描述了一名3.5岁女童，出现阴毛早现（根据坦纳分期为P2）、骨龄提前至6岁10个月以及血清17-羟孕酮（17-OHP）水平升高。使用聚合酶链反应/扩增产生限制位点（PCR/ACRS）方法对患者及其家庭成员进行了9种最常见的假基因衍生CYP21A2点突变的分子分析。我们在患者中检测到P30L/I172N基因型。她从母亲那里遗传了一个轻度的P30L突变，从父亲那里遗传了一个严重的I172N突变。结论：尽管CAH的表型由产生大部分酶活性的等位基因决定，并且预期应为轻度非经典（NC）表型，但已知更具男性化作用的轻度P30L突变可能在我们的患者中诱发了经典的SV表型。推荐剂量的氢化可的松持续治疗方案未能充分降低17-OHP水平。仔细调整剂量也无济于事，她的阴毛根据坦纳分期进展到了P3。该患者需要进行个体化定制治疗。
