Editorial: Rare Diseases: From Basic Science to Clinical Practice and Public Health

Lina Jankauskaite, MD, PhD ^1,2,3* Ozge Yilmaz ⁴ Urte Oniunaite ^1,2 Rasa Ugenskiene ⁵

• ¹ Lithuanian University of Health Sciences, Medical Academy, Pediatric Department, Lithuania, Kaunas, Lithuania
• ² Department of Pediatric, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Kaunas, Kaunas, Lithuania
• ³ Institute of Physiology and Pharmacology, Lithuanian University of Health Sciences, Kaunas, Lithuania
• ⁴ Manisa Celal Bayar University, Manisa, Manisa, Türkiye
• ⁵ Lithuanian University of Health Sciences, Medical Academy, Department of Genetics and Molecular Medicine, Kaunas, Lithuania

Rare diseases (RDs), characterized by their occurrence in a small por�on of the popula�on, have garnered significant aten�on as a burgeoning public health concern in recent years [1]. According to the Global Genes organiza�on, over 10,000 dis�nct rare and gene�c diseases affect approximately 400 million individuals worldwide. Unfortunately, half of the diagnosed with RD are children, and many of these condi�ons are either lethal or cause severe disabili�es. Since RDs are heterogeneous, complex, and individually rare, diagnosing and assessing them poses substan�al challenges, including delayed diagnosis, inadequate support systems, persistent disabili�es, and the lack of effec�ve treatment, o�en incurring substan�al financial costs [1]. It has been es�mated that up to 95% of rare diseases lack approved treatments by the Food and Drug Administra�on (FDA), with pa�ents typically wai�ng an average of 4.8 years for an accurate diagnosis [2].Accurate diagnosis and prompt treatment represent recurrent hurdles for healthcare professionals working with RD pa�ents. Advances in gene�c tes�ng and molecular biology have elucidated the pathogenesis of rare diseases and facilitated earlier diagnosis, leading to improved pa�ent outcomes [3]. Gene�c tes�ng expedites diagnosis and mi�gates healthcare expenditures by circumven�ng unnecessary inves�ga�ons, procedures, hospitaliza�ons, and medica�on regimens, ul�mately leading to the best possible pa�ent clinical outcomes [4]. Innova�ons such as gene�c modifica�ons and tradi�onal drugs have brought breakthroughs against gene�cally determined diseases [5] while emerging research areas such as oligonucleo�de therapy, stem cell therapy, and gene therapy have revolu�onized treatment paradigms for myriad complex diseases [3].The available op�ons remain limited given the significant scien�fic exper�se and investment capital required to develop rare disease treatments [3]. Nevertheless, recent years have witnessed an outburst in mergers and acquisi�ons, driven by novel incen�ves and mi�gatory measures [6]. Accelerated data analysis, integra�on, and aggrega�on of data facilitate the dissemina�on of informa�on, the development of treatments, and new interna�onal collabora�ve research endeavors, thereby streamlining efforts for researchers, clinicians, pa�ents, and their families [6]. Standardiza�on and streamlining of mul�site trial review and contrac�ng processes are crucial for enhancing pa�ent access to new therapies, leveraging extensive datasets to foster novel medical insights, and refining trial designs [5]. Thus, ini�a�ves like the Rare Diseases Clinical Research Network (RDCRN) or Rare Disease Europe (EURORDIS) encourage collabora�on among diverse stakeholders, providing training opportuni�es for new inves�gators in rare disease research [3]. Despite advances in technology, the 10-year survival rate post-diagnosis is s�ll approximately 80%, with a significantly higher risk of death for men [7].While developed countries experience significant advancements addressing rare diseases, inequali�es persist in less affluent regions, where access to healthcare improvements is limited, exacerbated by deficient public health infrastructure. Social customs and cultural prac�ces rooted in history and tradi�on can hinder progress, par�cularly in regions with deep tradi�ons [8]. Varying defini�ons of rare diseases according to disease frequency in different countries complicate interven�on strategies.Addressing rare diseases extends beyond pharmacotherapy to encompass holis�c pa�ent care, necessita�ng tailored interven�ons, symptom management, and environmental modifica�ons to accommodate pa�ent needs [8]. The mental health toll exacted by RD on affected children and their families is profound, precipita�ng psychological distress, diminished quality of life, heightened caregiver burden, and social upheaval [9] [10]. The prolonged diagnos�c journey, o�en culmina�ng in unmet therapeu�c needs, fosters prolonged uncertainty, fueling anxiety and emo�onal distress among pa�ents and caregivers [9,11]. Even when pa�ents have knowledge about their disease, knowing that the scien�fic knowledge of most rare diseases is lacking can increase anxiety about the future, create instability, and lead to various consequences for family members as well [11]. Addi�onally, caring for a sick child is highly �me-consuming (due to hospital visits, specialized treatments, and diagnos�c procedures since children require mul�disciplinary care coordina�on among mul�ple sectors and a high frequency of inpa�ent stays), compounded by financial strain and disrup�ons to familial dynamics, amplify emo�onal distress [10]. Siblings may feel overshadowed or neglected, giving up their free and leisure �me. Moreover, it is a real medical financial hardship. All of this leads to higher emo�onal distress. Children afflicted with RDs encounter formidable barriers, including compromised self-sufficiency and a lack of social support or understanding from others. They may also feel socially rejected and experience nega�ve emo�ons from trauma�c situa�ons (e.g. separa�on from their parents during long hospital stays) [9,10]. Unfortunately, many families do not know about psychosocial care services or do not have the �me to do so, which makes psychological well-being even worse [9].There is s�ll a small number of studies on the burden experienced by families of children with RD. At present, most family members report experiencing caregiver burden, which typically appears to increase in rela�on to the severity of the disease [12]. Because RD o�en starts in childhood, the burden of the disease and associated challenges most o�en fall on family members. Studies report that family members of individuals with RD's feel socially isolated and lonely (it is difficult for them to find other families facing the same disease and to share their caregiving burdens); they also struggle to find enough �me for themselves, it nega�vely impacts their work or occupa�on [12]. It is worth men�oning that having a child with a rare disease places an emo�onal burden on family members and caregivers; there is a correla�on between more debilita�ng forms of disease and a greater impact on family and their social life [12].Children with RD and their parents confront mul�faceted challenges, as exis�ng healthcare models do not adequately fulfill their medical and psychosocial needs. Communica�on barriers, compounded by speech and language disorders, impede daily care and social integra�on [11]. Therefore, it is crucial to have good access to home healthcare services. However, due to funding problems and a need for more human resources, these families need more access to these services even in North America and Europe [11].Children with RD and their families may encounter barriers to engagement in community ac�vi�es due to a lack of accessible transporta�on and other adapta�ons to meet mobility or other needs. This creates significant barriers to atendance at medical appointments, engagement in educa�onal and therapeu�c ac�vi�es, and play, implica�ng further adapta�on to fulfilled lives.In light of these challenges, several recommenda�ons are warranted:1. Ac�ve engagement of pa�ents, families, and communi�es in the research process. 2. Adop�on of a pa�ent-centered model by healthcare companies, leveraging digital and analy�cal technologies to personalize interven�ons. 3. To reduce the neglect and marginaliza�on of the RD popula�on, it is important to increase public awareness and competency in health and social care policies. 4. Comprehensive psychosocial assessments by healthcare providers to ensure appropriate support to pa�ents and their family members. 5. Centralising appropriate care, ensuring con�nuity, mi�ga�ng communica�on barriers, and enhancing access to specialist exper�se, looking more broadly at the child's health and well-being than just one aspect of care by interac�ng with different medical recommenda�ons from mul�ple specialists.These measures collec�vely aim to op�mize outcomes and enhance the quality of life for individuals afflicted with RDs and their families.