Resolved Neutropenia, Thrombocytopenia, and Premature Ovarian Insufficiency in a G6PC3-Deficient Patient Treated With an SGLT2-Inhibitor

Glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency is an ultrarare metabolic disorder characterized by congenital neutropenia and multisystem abnormalities and accumulation of 1,5-anhydroglucitol. We report a 28-year-old woman with G6PC3 deficiency, congenital neutropenia, cardiac and urologic abnormalities, and premature ovarian insufficiency treated with empagliflozin. Treatment by a gradual granulocyte colony–stimulating factor tapering strategy rapidly reduced 1,5-anhydroglucitol levels and resulted in recovery from neutropenia, allowing complete discontinuation after neutropenic relapse. Platelet counts increased and regular menstrual cycles resumed with normalization of gonadotropins, detectable anti-Müllerian hormone, and mid-luteal progesterone confirming ovulation. This case illustrates the impact of empagliflozin treatment on the recovery from neutropenia and thrombocytopenia, and resumption of ovarian function in G6PC3 deficiency.