Gonadic Function and Pubertal Development in Female Patients With Classic Galactosemia

Newborn screening for galactosemia and adherence to a galactose-free diet have greatly reduced acute neonatal symptoms, leading to high survival rates. However, despite good therapeutic compliance, long-term complications-especially primary ovarian insufficiency (POI) and its related morbidity-remain common. Because galactosemia is rare, identifying factors underlying ovarian dysfunction and fertility-preservation options has been challenging. A large, homogeneous multicenter Italian study could help clarify unresolved aspects of POI in females with classic galactosemia.

Primary aims:

• Compare clinical, auxological, and hormonal features of girls with galactosemia to those of the general population at key stages of pubertal development.
• Identify potential factors contributing to POI.
• Describe fertility-related characteristics in affected patients.

Secondary aims:

• Determine the proportion of patients who reach their familial height target.
• Assess quality of life and psycho-emotional adjustment.
• Evaluate psychomotor and cognitive development.

Inclusion criteria

• Female patients followed at participating Pediatric Endocrinology and Inherited Metabolic Disease Centers, born between January 1st, 1980 and December 31st, 2024, with a diagnosis of classic galactosemia and confirmed by genetic testing.
• Obtaining informed consent.

Exclusion criteria

• Patients with known chromosomal abnormalities (e.g., trisomy 21, Turner syndrome, Fragile X syndrome, Kabuki syndrome, or other genetic conditions associated with pubertal disorders);
• Patients with primary ovarian insufficiency due to causes other than galactosemia.