✅ Model Answer:
• Diagnosis: 46,XY DSD due to 5α-reductase type 2 deficiency (SRD5A2 mutation).
• Evidence: Ambiguous genitalia with palpable gonads, normal testosterone response to hCG, low DHT, elevated T/DHT ratio (>15), normal AMH (testicular tissue present), no uterus.
• Next step: Genetic testing (SRD5A2). Sex of rearing: often male (virilization at puberty). Testosterone therapy if needed for penile growth. Multidisciplinary care. Gonadal monitoring.

✅ Model Answer:
• Gene: SRD5A2 (steroid 5α-reductase type 2) located on chromosome 2p23.
• Inheritance: Autosomal recessive.
• Prevalence: Most common in populations with consanguinity (e.g., Dominican Republic, Papua New Guinea).
• Enzyme function: Converts testosterone to the more potent androgen dihydrotestosterone (DHT) in target tissues (external genitalia, prostate, skin).
• Pathophysiology: Loss-of-function mutations in SRD5A2 → deficient DHT production → impaired masculinization of external genitalia in utero. Wolffian duct development (dependent on testosterone) is normal, so internal male structures (epididymis, vas deferens, seminal vesicles) are present.
• Pubertal virilization: At puberty, testosterone increases and can produce virilization via the androgen receptor (though less potent than DHT), leading to male phenotype.

✅ Model Answer:
• Neonatal:
- Ambiguous genitalia: Clitoromegaly, labioscrotal fusion, microphallus, hypospadias, bifid scrotum.
- Palpable gonads (testes) in the labia or inguinal canal.
- Normal Müllerian regression (no uterus, due to AMH production).
- Male internal ducts present (epididymis, vas deferens).
• Puberty (if raised female):
- Virilization: Deep voice, muscle mass, hirsutism, penile growth, testicular descent (may occur).
- No breast development (unlike CAIS).
- Male gender identity often emerges in those raised female (due to androgen exposure).
• Fertility: May be reduced due to hypospadias and small phallus; sperm production is usually normal.

✅ Model Answer:
• Karyotype: 46,XY.
• hCG stimulation test: To assess Leydig cell function and androgen production.
- Testosterone (baseline and post-hCG): Normal or elevated.
- DHT (post-hCG): Low or absent.
- T/DHT ratio: >15 (normal <10).
• AMH: Normal or elevated (Sertoli cell function intact).
• Pelvic ultrasound: Absent uterus, testes present (inguinal or labial).
• Genetic testing: SRD5A2 gene sequencing (confirmatory).
• Rule out other causes: Androgen insensitivity (AR mutation), 17β-HSD deficiency (low T, low androstenedione).

✅ Model Answer:
• Sex of rearing:
- Traditionally: Often raised female, but many choose male due to pubertal virilization and male gender identity.
- Shared decision-making with family and multidisciplinary team.
• If raised male:
- Testosterone therapy: To promote penile growth (if needed).
- Hypospadias repair and orchidopexy.
- Monitor for spermatogenesis.
• If raised female:
- Gonadectomy before puberty (to prevent virilization).
- Estrogen replacement at puberty.
- Vaginal dilation or surgical vaginoplasty if needed.
• Psychological support: Important for gender identity and body image.

✅ Model Answer:
• Psychosocial: Gender identity confusion, body image issues, social stigma.
• Fertility: May be reduced (hypospadias, small phallus) but sperm production is often normal.
• Undescended testes: Risk of testicular malignancy (if not surgically managed).
• Virilization in females: If raised female and gonadectomy is delayed, virilization at puberty can occur.
• Psychological impact: Need for long-term counseling and support.

✅ Model Answer:
• Prognosis:
- Good with appropriate sex of rearing and hormone management.
- Male-raised: Good quality of life, normal testosterone levels, fertility possible.
- Female-raised: Good quality of life with estrogen replacement, but may need psychological support.
- Fertility: May be preserved with assisted reproductive techniques.
• Long-term follow-up:
- Monitor hormone levels.
- Monitor testicular health.
- Psychosocial support.
- Genetic counseling.

✅ Model Answer:
• 5α-Reductase deficiency:
- Enzyme: 5α-reductase type 2 (SRD5A2).
- Androgens affected: Testosterone to DHT conversion impaired.
- Lab findings: Normal T, low DHT, ↑T/DHT ratio.
- Pubertal virilization: Yes (via testosterone).
- Gene: SRD5A2.
• 17β-HSD deficiency:
- Enzyme: 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3).
- Androgens affected: Androstenedione to testosterone conversion impaired.
- Lab findings: High androstenedione, low testosterone, ↑A/T ratio.
- Pubertal virilization: Yes (due to peripheral conversion of androstenedione to testosterone).
- Gene: HSD17B3.