Researchers from Israel reported the first case of a woman who is transgender with Alagille syndrome (ALGS) who underwent gender affirmation treatment, as published in Transgender Health.

Gender affirmation therapy may include hormone therapy and surgical interventions. Hormone therapy is generally used to induce secondary sexual characteristics such as enlarged breasts and widened hips in women who are transgender. However, hormone therapy with estrogen can lead to an increase in liver enzymes as well as a disruption in bilirubin metabolism.

ALGS is a rare genetic disease caused by the dysfunction of the Notch signaling pathway, which is involved in numerous developmental processes. The disease is described by intrahepatic bile duct paucity leading to the buildup of bile in the liver and liver damage.

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Read more about ALGS overview

ALGS is inherited in an autosomal dominant manner, so children of both biological sexes have an equal chance of inheriting the disease if 1 of their parents is also affected. In around 50% of cases, ALGS is caused by spontaneous mutations during gametogenesis or embryonic development.

Patients who are transgender may already experience great distress because of the difference between the sex they are assigned at birth and their unaffirmed gender identity, the authors said.

“The case presented here is the first described [ALGS] transgender patient to undergo gender affirmation treatment, including [hormone treatment] and vulvo-vaginoplasty surgery,” they wrote.

Because of the strain that estrogen treatment causes on the liver, women who are transgender with a genetic disease such as ALGS may be under even more distress and should be followed and supported accordingly.


Shefler H, Berl A, Liran A. Transgender and Alagille syndrome: a rare case of a trans woman with Alagille syndrome. Transgender Health. Published online December 10, 2021. doi:10.1089/trgh.2021.0023