3-Beta-Hydroxysteroid Dehydrogenase Type II Deficiency (HSD3B2)
3-Beta-hydroxysteroid dehydrogenase type II deficiency is a pan-ethnic, autosomal recessive disorder caused by pathogenic variants in the HSD3B2 gene. This disease causes impaired hormone production and disrupted sexual development. The classic presentation of this disease has two forms: the salt-wasting and the non-salt-wasting types. Residual HSD3B2 enzyme activity determines whether an individual will have the salt-wasting or non-salt-wasting form. The salt-wasting type is characterized by a lack of salt reabsorption, which can be life threatening, and can present in early infancy with dehydration, poor feeding, and vomiting. Individuals with the non-salt-wasting type have low levels of sodium reabsorption and have milder symptoms. Males with either type can have ambiguous genitalia. Females can present with slight abnormalities of external genitalia at birth but typically do not present until puberty with irregular menstruation, premature pubic hair growth, or excessive body hair growth. Both males and females are typically infertile. Nonsense and frameshift variants that result in truncated proteins result in complete loss of enzyme activity and are typically associated with the salt-wasting form. Missense variants, which cause incomplete loss of enzyme activity, result in the non-salt-losing form. Life expectancy is variable, although the salt-wasting form of the disease can be fatal if not diagnosed and treated early.
For information about carrier frequency and residual risk, please see the residual risk table.