Research progress of 5α-reductase 2 deficiency / 国际儿科学杂志

Steroid 5α-reductase type 2 deficiency is caused by mutations in the SRD5A2 gene and is a congenital metabolic defect of autosomal recessive inheritance. The variety of gene mutations causes different levels of enzyme deficiency and results in different clinical phenotype,from the typical male sexual characteris-tics to the complete female sexual characteristics( small penis,perineal scrotal hypospadias and complete female phenotype). In puberty,the child with 5α-reductase 2 deficiency may undergo virilization. The correlation be-tween clinical phenotype and genotype is still under investigation. Steroid 5α-reductase type 2 deficiency and oth-er 46,XY disorders of sex development including androgen insensitivity syndrome have similar clinical charac-teristics,and 5α-reductase type 2 deficiency should be differentiated from other 46,XY disorders of sex develop-ment. The diagnosis of 5α-reductase type 2 deficiency is based on clinical manifestations,imaging examination, hormone detection,urinary steroid analysis and genetic testing,etc. The cutoff value of hormonal diagnosis still needs to be studied and the diagnosis should be further standardized. In most patients,the shift from female to male will occur around puberty,and may cause gender anxiety. The patient may have gender social identity crisis and other ethical controversies. In terms of treatment,gender assignment and gender role management are contro-versial,and surgical procedures need to be further studied. This paper reviews the clinical features,clinical pheno-type and genotype,the differential diagnosis,diagnosis basis and treatment strategy as well as the future challen-ges of 5α-reductase type 2 deficiency,in order to alleviate the sufferings caused by later gender transition in pu-berty and improve the quality of life.

The analysis of gene mutation and diagnosis and treatment of 5α-reductase 2 deficiency in a child / 临床儿科杂志

Objective To explore the clinical feature and gene mutation in steroid 5α-reductase 2 deficiency (SRD5A2). Method The clinical data of SRD5A2 in a child with vulva abnormality as the first manifestation was retrospectively analyzed. Results This was a 29-month-old child, whose social gender was female. The level of her basic luteinizing hormone (LH) was 0.07 mIU/mL, and follicle-stimulating hormone was (FSH) 0.39 mIU/mL. The baseline levels of testosterone (T), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17-OHP) and androstendione (A2) were 0.06 ng/mL, 19.67 pg/mL, 1.20 ng/mL, and 0.07 ng/mL respectively. Those levels were 3.65 ng/mL, 68.25 pg/mL, 51.72 ng/mL, and 14.70 ng/mL respectively after Human chorionic gonadotropin (HCG) stimulation. The levels of her anti-mullerian hormone (AMH) was 22.97 ng/mL, and inhibin B (INH-B) was 274.4 pg/mL. The uterus and ovaries were not detected by Pelvic ultrasound and MRI. The chromosome showed 46, XY. Sex determination (SRY) gene detection showed normal. Androgen receptor (AR) gene detection showed negative. There was pathogenic mutation of 5α-reductase 2 (SRD5A2) gene in peripheral blood of the child and her parents. The penis grows 2 cm after 4 months of treatment with 2.5% DHT gel. Conclusion SRD5A2 is diagnosed mainly based on the increase of T/DHT after HCG stimulation experiment and it can be confirmed by detection of pathogenic SRD5A2 mutation.

The correlation between phenotype and genotype of 5α-reductase 2 deficiency in 5 children / 临床儿科杂志

Objective To explore the correlation between phenotype and genotype of 5α-reductase 2 deficiency. Methods The clinical data of five children with 5α-reductase 2 deficiency were retrospectively analyzed and the relation between their clinical phenotype and genotype were analyzed. Results All of these five children presented small penis and testicular hypoplasia, three of whom had ones similar to the clitoris appearance. The testosterone/dihydrotestosterone (T/DHT) ratio was 10.26-64.99 after human chorionic gonadotropin (hCG) stimulation. Gene detection showed one case had c.680G>A homozygous mutation and the others were compound heterozygous mutations. The mutations were mainly missense mutations, followed by deletion, duplication and nonsense mutations. Conclusion The 5α-reductase 2 deficiency has different degrees of abnormal genital development. Genetic testing contributed to the diagnosis of this disease.