Manuscript 1.docx

Classical galactosemia is a rare inherited metabolic disorder requiring lifelong dietary restriction of galactose. Despite this, many patients struggle to maintain strict adherence, leading to poor clinical outcomes. This systematic review aimed to synthesize existing evidence on factors influencing dietary adherence in individuals with classical galactosemia. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted, and five studies were included. Data were extracted on study and participant characteristics, adherence outcomes, and influencing factors, with methodological quality appraised using the QUADL checklist. The findings revealed that adherence is shaped by a complex interplay of social, cultural, and emotional challenges, including stigma, social isolation, and the psychological burden of restrictions. Caregiver knowledge and attitudes were critical in supporting dietary management, particularly in young children. Nutritional factors, such as over-restriction of permissible foods, further limited dietary variety and posed challenges to adherence. Additionally, the conviction of health professionals regarding the necessity of strict restriction influenced patient practices. The included studies were all cross-sectional, small in size, and largely conducted in high and middle-income countries, limiting generalizability. These results highlight the need for culturally sensitive interventions and robust longitudinal research to strengthen the evidence base and improve adherence outcomes.<br>