Bertelloni Silvano, Baldinotti Fulvia, Russo Gianni, Ghirri Paolo, Dati Eleonora, Michelucci Angela, Moscuzza Francesca, Meroni Silvia, Colombo Ilaria, Sessa Maria R, Baroncelli Giampiero I
Adolescent Medicine, Pediatric Division, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
Sex Dev. 2016;10(1):28-36. doi: 10.1159/000445090. Epub 2016 Apr 13.
Clinical records (n = 24) with an established diagnosis of 5α-reductase-2 deficiency were reviewed. A previous misdiagnosis was present in about 70% (period from first observation to definitive diagnosis: 9.1 ± 10.8 years), and in 8 children gonadal removal was performed before certain diagnosis. Initial sex assignment was female in 16/24 (67%) and male in 8/24 (33%) cases. After diagnosis, sex re-assignment was performed in 5 babies (4 girls to male sex; 1 boy to female sex). Baseline testosterone/DHT ratio was diagnostic in 6/12 subjects (first months of life n = 4; puberty n = 2), while post-hCG testosterone/DHT ratio was diagnostic in all tested individuals (choosing both the cut-off value 15 or 10). Eighteen different mutations in the steroid-5α-reductase-2 (SRD5A2) gene were identified, 5 of which have never been reported. In conclusion, a time lag exists before the diagnosis of 5α-reductase-2 deficiency is established; sex assignment and gonadal removal may be performed before certain diagnosis. Sex re-assignment is usually female to male, but the contrary may occur. A large variability in clinical phenotypes and genetic mutations was present in this cohort. Accurate endocrine evaluation is recommended in babies possibly affected by 5α-reductase-2 deficiency, since the use of appropriate cut-off values of testosterone/DHT ratio after hCG stimulation may permit to select individuals for SRD5A2 gene analysis. A genotype-phenotype correlation was not found in this study.
回顾了24份确诊为5α-还原酶-2缺乏症的临床记录。约70%的病例曾有过误诊（从首次观察到确诊的时间：9.1±10.8年），8名儿童在确诊前进行了性腺切除。初始性别指定为女性的有16/24例（67%），男性的有8/24例（33%）。确诊后，5名婴儿进行了性别重新指定（4名女孩变为男性；1名男孩变为女性）。6/12名受试者的基线睾酮/双氢睾酮比值具有诊断意义（出生后头几个月4例；青春期2例），而所有受试个体注射人绒毛膜促性腺激素（hCG）后的睾酮/双氢睾酮比值均具有诊断意义（选择临界值15或10）。在类固醇5α-还原酶-2（SRD5A2）基因中鉴定出18种不同突变，其中5种从未报道过。总之，在确诊5α-还原酶-2缺乏症之前存在时间延迟；性别指定和性腺切除可能在确诊前进行。性别重新指定通常是从女性变为男性，但也可能相反。该队列中临床表型和基因突变存在很大差异。建议对可能受5α-还原酶-2缺乏症影响的婴儿进行准确的内分泌评估，因为在hCG刺激后使用适当的睾酮/双氢睾酮比值临界值可能有助于选择进行SRD5A2基因分析的个体。本研究未发现基因型与表型的相关性。
