5-alpha reductase deficiency: what it is, how it shows up and how it is managed

The NHS describes differences in sex development (DSD) as a group of rare conditions involving genes, hormones and reproductive organs, including the genitals, in which a person's sex development is different from most other people's. It lists several types, and explains that some people have chromosomes usually associated with being male (XY) but reproductive organs and genitals that may look different from usual because of a difference in their genes or in how they respond to sex hormones, or both.

MedlinePlus Genetics, a US National Library of Medicine resource, describes 5-alpha reductase deficiency as a condition that affects sexual development before birth and during puberty. People with it are genetically male, with testes, but their bodies do not produce enough of a hormone called dihydrotestosterone, or DHT. DHT has a critical role in male sexual development, and a shortage of it disrupts the formation of the external sex organs before birth. The same condition appears under other names, including pseudovaginal perineoscrotal hypospadias, and the Genetic and Rare Diseases Information Center lists it as 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.

The NHS page on DSD does not discuss this specific condition by name, and no UK patient leaflet specific to 5-alpha reductase deficiency was available when this page was prepared. The condition-specific detail below therefore comes from MedlinePlus Genetics, and the description of how DSD is assessed and supported in the UK comes from the NHS.

MedlinePlus explains that variants in the SRD5A2 gene cause the condition. The gene provides instructions for making an enzyme called steroid 5-alpha reductase 2, which converts testosterone to DHT. DHT is essential for the normal development of male characteristics before birth, particularly the formation of the external genitalia. When the enzyme does not work effectively, the developing reproductive tissues do not receive enough DHT.

The condition is inherited in an autosomal recessive pattern, which means both copies of the SRD5A2 gene must have a variant. The parents each carry one copy of the altered gene but typically show no signs. MedlinePlus adds that people who are genetically female may inherit variants in both copies of the gene, but their sexual development is not affected because the development of female sex characteristics does not require DHT.

The condition is rare and the exact incidence is not known. MedlinePlus notes that large families with affected members have been found in several countries, including the Dominican Republic, Papua New Guinea, Turkey and Egypt.

There is no single typical appearance. MedlinePlus says that many people with 5-alpha reductase deficiency have external genitalia that appear female. In other cases, affected infants have male-typical external genitalia, often with an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias). Still others have genitalia that do not look clearly male or clearly female.

The NHS says that the most common times to find out that a person has a DSD are around the time of birth or when someone is a teenager. Doctors check a baby for DSD soon after birth because of signs such as undescended testicles or genitals that look different. In an older child, the NHS says a DSD may be diagnosed if the child does not go through puberty properly, for example if puberty changes do not start or periods do not begin.

MedlinePlus describes that during puberty an increase in male sex hormone levels leads to the development of some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair and a growth spurt. The penis and scrotum may grow larger. People with the condition do not develop much facial or body hair.

Researchers believe people with the condition develop these characteristics in response to the higher testosterone produced by the testes at puberty, and some affected people retain a small amount of enzyme activity that may produce DHT and contribute. The NHS notes that some people with DSD may need hormone therapy and psychological support, and some may want to think about altering their existing genitals, for example by using vaginal stretch techniques. Some consider surgery, and the NHS frames these as personal decisions to be discussed with the specialist team.

Fertility is an important topic. MedlinePlus says most affected individuals are unable to have biological children without assisted reproduction. The NHS says that if you have a DSD and want to explore parenthood, you can discuss this with your specialist care team.

The NHS lists the tests that may be done to get a clear diagnosis of DSD in a baby: a further physical examination by a specialist, an ultrasound scan to examine the internal organs, and blood tests to check genes and hormone levels. In England, it says you need to register a baby's birth within 42 days, which is usually enough time to complete the tests, discuss the results with the care team and identify the baby's sex.

For a specific diagnosis such as 5-alpha reductase deficiency, MedlinePlus lists genetic testing information, and the condition is defined by changes in the SRD5A2 gene. In the UK, the NHS says an older child with suspected DSD is usually referred by a GP to a consultant paediatric endocrinologist or an adolescent gynaecologist.

The NHS says a team of specialist healthcare professionals will work with you to understand the condition and offer support and advice. A specialist nurse in the care team can help you learn about DSD, and a psychologist can help you address concerns including sexuality, relationships and body image. Many forms of DSD do not require any medical care other than understanding the baby's development and knowing what to expect as they grow older.

The NHS also says you can stay with the gender linked to your sex at birth, which is the sex on your birth certificate, but if your legal sex does not represent who you are or how you identify, you can discuss your options with your care team. National support groups it names include the Congenital Adrenal Hyperplasia Support Group and DSD Families. Speaking with others who have lived experience is often valued by families and by adults with DSD.

Care for DSD is usually delivered through specialist NHS multidisciplinary teams because the condition is rare and involves endocrinology, genetics, surgery, psychology and nursing together. A GP can refer you or your child. Private routes exist for some elements, such as endocrinology consultations or genetic testing, but the team approach described by the NHS is the model most people follow.