Table 3.

Barriers and facilitators to optimal care.

Ecological Model of Health-Levels	Studies	Barriers	Facilitators
Intrapersonal	Bogart (2015) [37], Hanson (2018) [53], Magliano (2013) [48], Mazzella (2021) [54], Vines (2018) [32]	Limited knowledge of patients and families Limited self and family education Limited self-esteem and stress-coping mechanisms	Information-sharing between parents and doctors, doctors and patients
Interpersonal	Anderson (2013) [35], Baumbusch (2018) [12], Boettcher (2020) [50], Bogart (2015) [37], Currie and Szabo (2019) [13], Damen (2022) [51], Gimenez-Lozano (2022) [11], Gómez-Zúñiga (2019) [46], Huyard (2009) [47], Pasquini (2021) [55], Smits (2022) [40], Verger (2021) [31]	Scarce knowledge of healthcare stakeholders (medical and paramedical personnel, community services personnel, insurance representatives and other parties) Lack of awareness of school staff Limited awareness in society groups (schoolmates, peer groups, parents’ relatives, employers and colleagues)	Supported self and parental care Patients’ dynamic groups and advocacy organizations Rare Disease Awareness and Assistance Programs
Institutional/ Organizational	Adama (2021) [34], Anderson (2013) [35], Baumbusch (2018) [12], Boettcher (2020) [50], Currie and Szabo (2019) [39], Currie and Szabo (2019) [13], Gao (2020) [57], Geerts (2008) [52], Gimenez-Lozano (2022) [11], Gómez-Zúñiga (2019) [46], Huyard (2009) [47], Mazzella (2021) [54], Palacios-Ceña (2018) [49], Pasquini (2021) [55], Sisk (2022) [56], Smits (2022) [40], Somanadhan and Larkin (2016) [41], Witt (2019) [33]	Structures Lack of genetic laboratories, facilities and tests to establish an early diagnosis Geographically distributed health and social services Centers of expertise mainly placed in tertiary levels of care or non-existent National registries complex, incomplete or non-existent Limited industry conducting research on orphan drugs Shortage of expert professionals in all fields (doctors, nurses, speech therapists, ergo therapists, play therapists, psychologists, technicians, etc.) Processes Limited RD education in general doctors and primary care personnel Lack of protocols/guidelines for clinical management and follow-up Disconnection between primary, secondary and tertiary level of care Information not effectively shared among all professionals involved Outcomes Inequity and inaccessibility in holistic care Dissatisfied parents emotionally and financially burnt out Patients with frequent relapses, hospitalizations, deterioration and unmet needs Mistrust in the healthcare system and the government	Structures Rare Disease Centers of Expertise geographically planned Genetic services and counseling accessible Processes Well-educated physicians, nurses and other professionals National registries taxonomized for each group of diseases linked with appropriate medications’ prescriptions and other treatments Single entry point and official healthcare coordinator Outcomes Better services for patients and optimized health outcomes Psychosocial care for patients and families
Community	Baumbusch (2018) [12], Gimenez-Lozano (2022) [11], Pasquini (2021) [55], Verger (2021) [31]	Inadequate communication between family members and local authorities Absence of single entry point and official care coordinator School staff uneducated, absence or inadequacy of school nurses, unsafe school environment	Community-based interventions/Rare Disease Assistance Programs Equipped local health services Educated primary healthcare physicians Designation of formal healthcare coordinator Pragmatic healthcare plan Collaboration with school personnel and school nurses
Public and Policy	All 25 selected studies [12,13,31,32,33,34,35,36,37,38,39,40,41]	Lack of public funding Lack of industry interest due to the scarcity of knowledge and rarity of the disorders Limited university/academic/research funding and programming for RDs Theoretical approaches not linked to actual methods and intervention programs Restricted integration and evaluation policies for healthcare services involved	Public funding Expanding neonatal screening tests Primary healthcare awareness and education Comprehensive healthcare planning starting from first day of diagnosis