Integrative Network View of PCOS: Organ Crosstalk Driven by the Hyperandrogenemia-Insulin Resistance-Inflammation Triad.

Rare diseases (RDs) are conditions that affect a small number of individuals compared to more common illnesses. It is defined as fewer than 200,000 people in the United States (Commissioner, ) and fewer than 5 in 10,000 in the European Union (European Commission, ). Although individually rare, RDs collectively affect millions of people worldwide. Approximately 70% of RDs manifest in childhood and often involve complex physical, cognitive, and developmental challenges (The Lancet Diabetes Endocrinology, ; Nguengang Wakap et al., ). Many children with RDs live with ongoing disability, delayed diagnosis, and limited treatment options (Bavisetty et al., ; Marimpietri & Zuccari, ; Witt et al., ), creating a significant burden on their physical health, emotional wellbeing, daily functioning, and family life (Schieppati et al., ; Verhoof et al., ). Understating the full impact of these conditions requires a holistic perspective. Health-related quality of life (HRQoL) provides such a framework by capturing an individual’s subjective perception of their wellbeing across physical, emotional, and social domains (Hays & Reeve, ). In contrast to clinical assessments that focus primarily on symptoms, HRQoL integrates the psychosocial aspects of a patient’s experience. Grounded in theoretical frameworks like the Wilson and Cleary model, which links biology, symptoms, functioning, and environmental factors to overall health outcomes (Wilson & Cleary, ), HRQoL research provides critical insights into how children adapt to the challenges of living with an RD. Research from different settings consistently shows that children with RDs report lower HRQoL than their peers in the general population (Gao et al., ; Ries et al., ; Thomas et al., ; Yamaguchi et al., ), especially in the domain of physical functioning (Arrington-Sanders et al., ; Britto et al., ; Palermo et al., ). The majority of literature come from Western settings, where the psychosocial impact on the child is a key theme (Adama et al., ). For example, a study from Australia reported that around half of children with rare diseases experienced mental difficulties at school (Belzer et al., ). There is also an emphasis on the economic and emotional burden on caregivers which in turn affects child HRQoL(Buckle et al., ; Domaradzki et al., ; Dumbuya et al., ). Evidence from Asia, while growing, primarily focuses on the impact of socioeconomic factors and treatment availability on HRQoL (Gao et al., ; Ng et al., ; Qi et al., ; Zhu et al., ). For instance, a nationwide study from China identified poverty and diagnostic delay as key contributors to disease burden encompassing impaired HRQoL (Yu et al., ). These focuses likely reflect the relatively limited medical resources and support systems in Asian regions, which may heighten the burden of RDs (Rodrigues et al., ). Emerging evidence indicates that cultural norms around family roles, child autonomy, and emotional expression influence children’s HRQoL (Kang et al., ; Mousavi et al., ; Satriono et al., ; Zhu et al., ). Together, these findings suggest the importance of evaluating HRQoL within specific healthcare and cultural context to inform targeted support and policy.