Newborn screening and a galactose-free diet have improved early outcomes in galactosemia, but long-term issues such as primary ovarian insufficiency (POI) remain significant. This study aims to clarify clinical, hormonal, developmental, and fertility-related factors in affected girls through a large multicenter Italian cohort.

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.

Female patients followed at the participating Italian Centers of Pediatric Endocrinology and Inherited Metabolic Diseases, born between January 1980 and December 2024, with a genetically confirmed diagnosis of classic galactosemia. The observation period will continue for all participants until adulthood, expected by December 2041.