Steroid 5α-reductase 2 deficiency syndrome

　　The gene analysis of patients with steroid 5α-reductase 2 deficiency syndrome shows some mutations, with missense mutations being more common and frame shift, splicing site, and nonsense mutations being less common. Approximately 75% are homozygous mutations, and 25% are heterozygous mutations. The mutation results in a decrease in the affinity of the enzyme for coenzyme NADPH or the binding ability to testosterone.

　　Steroid 5α-reductase (SRD5A) has 2 isozymes, namely SRD5A1 and SRD5A2. The two have 50% amino acid homology, located in the mitochondria, with NADPH as a cofactor, catalyzing the conversion of testosterone to the more potent DHT. The SRD5A1 gene is located at 5p15, with 5 exons, the optimal pH value is alkaline, and it is expressed in the liver and non-reproductive skin. The SRD5A2 gene is located at 2p23, with 5 exons, the optimal pH value is acidic, and it is mainly expressed in reproductive skin and prostate. The enzyme activity in the liver decreases gradually with age, and the enzyme activity in non-reproductive skin cannot be detected after 3 years of age.

　　Due to the significant changes in patients with the 5α-reductase 2 deficiency syndrome at birth and after puberty, their gender orientation is almost female at birth and male after puberty, which may lead to psychological problems related to gender identity. Male infants have a clitoral-like small penis that curves downward, perineal urethral fistula, blind pouch vagina, and separation of the vaginal orifice and urethral orifice.

　　The clinical manifestations of patients with this disease are heterogeneous. About 55% of patients have perineal urethral fistula and pseudo-vagina, while the rest can be urinogenital sinus retention, penile urethral fistula, or even small penis and penile urethra. The specific introduction is as follows:

　　1, Reproductive system

　　The reproductive system is characterized by ambiguous external genitalia, small penis, perineal urethral fistula, blind pouch vagina, absent or underdeveloped prostate, testicles located in the inguinal canal or labio-scrotal fold. They are often raised as females at birth.

　　2, Puberty development

　　Puberty starts normally, and progressive masculinization occurs, including voice deepening, increased muscle mass, penile enlargement, but without pubic, axillary hair growth or sparsity, no acne, no recession of the hairline at the temples and forehead, and generally no male breast development in most patients. After puberty, many patients change their gender to male.

　　Early diagnosis of the 5α-reductase 2 deficiency syndrome is very important for determining gender orientation as soon as possible. In most cases, the enzyme activity of SRD5A2 gene mutations does not exceed 0.4%, and in a few patients, the enzyme activity can be preserved at 3% to 15%. These patients have a relatively complete masculinization of the external genitalia, which is enough to determine the baby's gender as male at birth. Considering the developmental tendency of gender transition during puberty, making a correct diagnosis in the neonatal period is important for gender determination.

　　The 5α-reductase 2 deficiency syndrome is mostly caused by heredity, and the routine examination items are as follows:

　　1, The serum testosterone level of patients significantly increases after puberty, but the DHT level does not increase proportionally, and the T/DHT ratio can reach as high as 35-84 (normal adult males are 12±3.1), and the serum LH and FSH levels are normal or slightly elevated.

　　2, The ratio of 5α-and 5β-reductases of C19-steroids (such as androstenedione/androstane) in the urine of heterozygous patients is moderately elevated.

　　3. Genetic gene testing.

　　There are no special dietary requirements for 5α-reductase 2 deficiency syndrome, and a normal diet is generally sufficient. It is important to ensure a rich and balanced diet, meeting the needs of calories, proteins, vitamins, and other nutrients required for normal human metabolism. Appropriately increase the intake of vegetables, fruits, lean meat, fish, milk, and soy products. In terms of health care, it is important to relax, build confidence, maintain a good mental state, and actively cooperate with the doctor's treatment.

　　Early diagnosis of the 5α-reductase 2 deficiency syndrome is very important for determining gender orientation as soon as possible. In most cases, the enzyme activity of SRD5A2 gene mutations does not exceed 0.4%, and in a few patients, the enzyme activity can be preserved at 3% to 15%. These patients have a relatively complete masculinization of the external genitalia, which is enough to determine the baby's gender as male at birth. Considering the developmental tendency of gender transition during puberty, making a correct diagnosis in the neonatal period is important for gender determination.

　　Someone reported a case of a 9-month-old child with 5α-reductase 2 deficiency, using 2% DHT cream applied to the abdomen, 25mg/d, after 12 days the serum DHT level was 2.0mol/L (58g/dl), reaching the normal range of adult males. After 4 months of treatment, the penis length increased by 2cm (from 1.8 to 3.8cm), and no adverse reactions were found. At the same time, a penile urethroplasty or hypospadias repair should be performed. However, DHT treatment is still in the experimental stage, and there is no formal product on the market, and its long-term efficacy and safety are yet to be determined.

　　For adult patients, intramuscular injection of testosterone esters (such as testosterone enanthate, testosterone undecanoate, etc.) at supraphysiological doses (250-500mg/week) can bring the serum DHT level to the normal range and has some effects of enhancing masculinization, while performing male-oriented整形 of the external genitalia.

　　If raising as a female, the external genitalia need to be feminized, and both testicles should be removed at the same time. Estrogen replacement therapy should be given after the age of puberty.