Endocrine Abstracts (2016) 45 P45 | DOI: 10.1530/endoabs.45.P45

5-alpha reductase deficiency: insights into the diagnosis and management of a rare condition

Elena Monti1, Elim Man1, John Torpiano2, Gill Rumsby3, Polly Carmichael1, Helen Storr4, Caroline Brain1, Charles Buchanan5, Gerard Conway3, Helen Spoudeas1, Imran Mushtaq1, Khalid Hussain1, Ieuan Hughes6, James Greening7, John Achermann1 & Mehul Dattani1


1Great Ormond Street Hospital, London, UK; 2Mater Dei Hospital, Msida, Malta; 3University College Hospital, London, UK; 4Barts and The London Children’s Hospital, London, UK; 5King’s College Hospital, London, UK; 6University of Cambridge, Cambridge, UK; 7Leicester Royal Infirmary, Leicester, UK.


Introduction: 5-alpha reductase deficiency (5aRD) is a rare cause of 46XY DSD, that affects sex development before birth and during puberty. The incidence is unknown; affected individuals have been described from all around the world, particularly in small communities or where consanguinity is common.

Methods: A 20-year retrospective review of presenting features, biochemical data and genetic analysis of all patients presenting to a single multidisciplinary team was undertaken.

Results: In total, 15 patients with a wide phenotypic spectrum were identified. Thirteen were diagnosed in infancy; two presented with androgenisation in adolescence. Of those presenting earlier, six were raised male, six female and one changed from female to male in early childhood. Two individuals presenting in adolescence had been raised female and one changed to male at this time. Traditional investigations including hCG testing were generally informative but required prolonged stimulation in childhood in order to get a diagnostic T:DHT ratio (baseline ratios were informative in the 3 teenagers, 3days HCG in 7/9 children). Urine steroid profile (USP) showed false negative results in the neonatal period (n=2) but was diagnostic after the age of 4–6 months with elevated ratios of 5alpha:5beta metabolites (12/15) and in one case it was sufficient to direct, alone, the genetic diagnosis. Two children had a family history of 5aRD and eight had documented consanguinity. Genetic analysis was informative in all children where available, with population hotpots of p.Arg246Gln in Pakistani (n=4) and c.332_333delTC in Malta (n=3). Three children raised female had early gonadectomy but more recently, gonads were left in pending detailed psychological counselling and gender identity assessment, occasionally necessitating the use of GnRH analogues. DHT cream +/− high dose testosterone was used to enhance penile size, with variable effect, in several males.

Conclusion: is a rare condition with variable presentation and course, but extremely important to diagnose as personalised management and support is needed. After the first 6 months of life, USP and early genetics can be diagnostic without the need for prolonged stimulation tests. As a subset of children can change their gender identity, careful interdisciplinary support is needed throughout childhood and adolescence.