Steroid 5α-reductase 2 deficiency syndrome
Introduction
Introduction to steroid 5-reductase 2 deficiency syndrome Abnormalities in any step of the action of androgens in the target cell can cause the effects of androgen not fully expressed and male pseudohermaphroditism. The process of androgen involves the reduction of testosterone by steroid 5-reductase 2 to DHT, testosterone and DHT. Binding to the androgen receptor (AR), localization and transcription of androgen-receptor complexes in hormone response elements. There are two main types of androgen resistance syndrome. One is the abnormal metabolism of testosterone in target cells, namely steroid 5-reductase 2 deficiency syndrome. The other is AR abnormalities, including testicular feminization and Reifenstein syndrome. basic knowledge The proportion of illness: 0.0008% Susceptible people: no special people Mode of infection: non-infectious Complications: testicular feminization
Cause
Etiology of steroid 5-reductase 2 deficiency syndrome
(1) Causes of the disease
The genetic analysis of patients with this disease shows a little mutation, more common as a missense mutation, rare deletion, shear point and nonsense mutation, about 75% are homozygous mutations, 25% are heterozygous mutations, the result of mutation is to make the enzyme The affinity for the coenzyme NADPH or the ability to bind to testosterone is reduced.
(two) pathogenesis
Steroid 5-reductase (SRD5A) has two isoenzymes, SRD5A1 and SRD5A2. The amino acid series of the two are 50% homologous. They are located in microsomes and use NADPH as a cofactor to catalyze the conversion of testosterone to a more potent DHT. The SRD5A1 gene is located at 5p15 and has 5 exons. The optimum pH is alkaline. It is expressed in liver and non-genital skin. The SRD5A2 gene is located at 2p23 and has 5 exons. The optimum pH is acidic. In the genital skin and prostate, the enzyme activity in the liver gradually decreases with age, and the enzyme activity of non-genital skin can not be measured after 3 years old.
Prevention
Steroid 5-reductase 2 deficiency syndrome prevention
There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease.
Complication
Complications of steroid 5-reductase 2 deficiency syndrome Complications testicular feminization
Because the patients have great changes at birth and after puberty, their gender orientation is almost always raised by girls at birth, and later changed to male life after puberty, which tends to cause feminization of testicles and may lead to gender identity. Psychological problems.
Symptom
Symptoms of steroid 5-reductase 2 deficiency syndrome Common symptoms Male blister pocket vagina
The typical performance of homozygous patients is 46, XY male infants with clitoris-like small penis, and bent downward, perineal hypospadias, blind pocket vagina, vaginal opening and urethral septum, normal testicular differentiation, located in the inguinal canal or labia scrotum Inside the pleats, there are epididymis and vas deferens, no uterus and fallopian tubes, ejaculatory ducts open in vaginal blind pockets, prostatic dysplasia, to puberty, serum testosterone reaches normal adult male level, patients appear varying degrees of masculinity: voice change, muscle capacity increase The penis is enlarged, the highest record is up to 8cm long, there is erection and libido, the skin and scrotum of the labia are increased, accompanied by hyperpigmentation, the testicles increase and fall into the labia sac pleats, but no man's breast development, no hemorrhoids, There is no forehead hairline retreat, beard, mane and pubic hair are absent or rare, the prostate does not appear corresponding development and growth, testicular histology shows that Ryd cells proliferate, spermatogenesis is absent or severely damaged, semen volume, viscosity, sperm Density and vitality Most patients are abnormal and a few patients can be normal.
The clinical manifestations of patients with this disease are heterogeneous, about 55% of patients have perineal hypospadias and false vagina, and the remaining patients may be urogenital sinus retention, penile hypospadias or even small penis and penis urethra.
Examine
Examination of steroid 5-reductase 2 deficiency syndrome
Patients had a significant increase in serum testosterone levels after puberty, but DHT levels did not increase proportionally, T/DHT ratios were as high as 35-84 (12 ± 3.1 for normal adult men), and serum LH and FSH levels were normal or slightly elevated. high.
Heterozygous patients have a moderate increase in the ratio of 5- and 5-reductants (eg, androstenone/prostan-2) in the urine of C19-steroids.
Genetic testing.
Diagnosis
Diagnosis and identification of steroid 5-reductase 2 deficiency syndrome
Diagnosis of steroid 5-reductase 2 deficiency is not an easy task. All prepubertal male pseudohermaphroditism or male pseudohermaphroditism masculinization in adolescence and no men's breast development should consider the possibility of this disease. Sex, the key to determining the diagnosis is to confirm an increase in the T/DHT ratio.
The diagnosis of steroid 5 reductase II deficiency is based on typical clinical manifestations, family history and characteristic endocrine changes. Prepubertal children are not easy to diagnose, especially in the absence of family history data, such as external genital malformations, small penis, perineum Scrotal hypospadias, testis located in the inguinal canal or labia scrotum pleats, chromosome karyotype 46, XY, highly suspected of this disease, can be clearly diagnosed by HCG test, the method is HCG 2000U, intramuscular injection once every other day, a total of 3 Second, before and after injection, plasma testosterone, DHT and/or urine 5-4 hydrocortisol (5-THF), 5-4 hydrocortisol (5-THF), 5-4 hydrocorticosterone (5-THB), 5-4 hydrocorticosterone (5-THB), prostanbulone (ETI) and androstenone (AND), T/DHT ratio after injection in patients with this disease or 5-THF/5-THF, 5-THB/ The ratios of 5-THB and ETI/AND were significantly higher than those of normal children of the same age. The change of 5-steroid metabolite/5-steroid metabolite ratio was mainly due to the reaction of liver 5-reductase activity, which was mainly formed in the liver. A small part is metabolized in peripheral tissues.
In prepubertal patients with intramuscular injection of chorionic gonadotropin (HCG) 1500 U / (m2 · d) for 3 consecutive days, normal male infants (17 days to 6 months) T / DHT ratio of 5.2 ± 1.5, prepubertal boys (6 months to 14 years old) was 11±4.4, and the patient's disease was significantly increased. The normal range of T/DHT ratio after puberty was 12±3.1, and the ratio of patients with this disease was 35-84.
