17-Beta Hydroxysteroid Dehydrogenase III Deficiency

17-Beta Hydroxysteroid Dehydrogenase III Deficiency

OMIM number: 264300

Comments closing date: 15/05/2025

17-beta hydroxysteroid dehydrogenase 3
deficiency is a rare genetic condition that affects
development of the external genitalia causing XY
disorder of sexual development (DSD), sometimes
previously called sex-reversal. This is where a
person has an X and Y chromosome but does not
have normal male genitalia as expected.
Chromosomes are the structures our genes are
packaged onto and usually males have an X and a
Y chromosome and females have two X
chromosomes. This condition only affects people
with XY chromosomes. 17-beta hydroxysteroid
dehydrogenase 3 is an enzyme that converts a
chemical called androstenedione, which is a
precursor of testosterone, into testosterone. A
fetus with an alteration on both copies of the
causative gene (HSD17B3) is unable to produce
the enzyme, or can only produce a very small
amount. If they have an XY karyotype
(chromosome make-up) they will be affected with
XY DSD. Testosterone is needed for fetuses with
XY chromosomes to develop male external
genitalia. As affected XY individuals are unable to
produce sufficient levels of testosterone their
external genitalia usually appear typically female
at birth or female with enlargement of the clitoris
and / or swellings in the groin which are testes. A
small number of affected babies have ambiguous
genitalia where it is not possible to say if they are
male or female. In a very small number the
genitalia appear male but are underdeveloped with
a small penis, often with hypospadias where the
urethral opening (hole for urine to exit) is
underneath the penis or where the penis joins the
scrotum, rather than at the tip of the penis.
Affected individuals do not have a uterus (womb).
Some affected individuals are diagnosed at birth
due to their sex being different to antenatal genetic
tests done for another reason (e.g. an increased
chance of Down syndrome), or because the genitalia look unusual. As most have genitalia that
look typically female most are raised as girls.
However, at puberty there is a surge in male
hormones which leads enlargement of the clitoris
and labia (virilisation) and sometimes other signs
seen in normal male puberty such as deepening of
the voice and facial hair development. It may only
be at this stage that the condition is diagnosed.
Some people choose to remain as female but
some change gender to male at this time. This can
have immense psychological and mental health
ramifications. The gonads (testes) are usually in
the groin area or within the abdomen which
increases the chance of developing a tumour
which can be cancerous. In view of this and
pubertal virilisation some individuals raised as girls
have their testes removed in childhood. If the
testes are not removed some individuals may be
able to produce sperm which can be removed
surgically, but many have reduced fertility or are
infertile.

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