Deciphering Androgen Action in a Child with 5α-Reductase Deficiency

Case Study:

Patient: John, a 7-year-old boy, was referred to the pediatric endocrinology clinic by his pediatrician due to concerns about delayed puberty and ambiguous genitalia. John was born with external genitalia resembling female anatomy, despite having XY chromosomes.

History: John’s mother reported normal prenatal development and delivery. He had no significant medical history but had never shown any signs of puberty, like facial hair growth or voice deepening.

Physical Examination: Upon examination, John displayed feminine external genitalia with labioscrotal folds and a clitoromegaly. Pubic hair was absent, and his chest was prepubertal. Testicular development was not palpable in the inguinal canals.

Investigations:

• Karyotyping: Confirmed a 46,XY karyotype, indicating male genetic sex.
• Hormonal assays: Revealed:
  • Elevated testosterone levels
  • Undetectable dihydrotestosterone (DHT) levels
• Ultrasound: Detected small testes present bilaterally in the inguinal canals.
• Genetic testing: Identified a homozygous mutation in the SRD5A2 gene, confirming complete 5α-Reductase deficiency.

Diagnosis: Complete 5α-Reductase deficiency (pseudohermaphroditism)

Management:

• John’s parents were counseled about the diagnosis and its implications.
• A multidisciplinary team, including specialists in pediatric endocrinology, urology, and genetics, was involved in his care.
• Testosterone replacement therapy was initiated to promote masculinization and stimulate testicular descent.
• Surgery to reposition the testes into the scrotum (orchiopexy) was recommended for future consideration.
• Psychological support was provided to help John and his family cope with the emotional challenges of the diagnosis.

Prognosis:

With proper management, John can live a healthy and fulfilling life. Testosterone therapy will help him develop secondary male sex characteristics and potentially achieve fertility. Regular monitoring and support will be crucial throughout his life.

Case Discussion:

John’s case highlights the critical role of 5α-Reductase in male development. The complete deficiency of this enzyme led to ambiguous genitalia and delayed puberty. Early diagnosis and intervention with hormone therapy were crucial in promoting masculinization and improving John’s quality of life.

This case also emphasizes the importance of:

• Genetic testing: For definitive diagnosis and family counseling.
• Multidisciplinary approach: Collaboration between specialists provides comprehensive care.
• Psychological support: To address the emotional and social challenges associated with the condition.

  https://drzaar.com/navigating-the-acth-enigma-in-a-young-girl-with-cah/