Although rare diseases have become a major public health issue, there is a paucity of population-based data on rare diseases. The aim of this epidemiological study was to provide descriptive figures referring to a sizable group of unrelated rare diseases.

Background: Despite the fact that a considerable number of patients diagnosed with childhood-onset rare diseases (RD) survive into adulthood, limited information is available on the epidemiology of this phenomenon, which has a considerable impact both on patients’ care and on the health services. This study describes the epidemiology of transition in a population of RD patients, using data from the Veneto Region Rare Diseases Registry (VRRDR), a web-based registry monitoring since 2002 a consistent number of RD in a defined area (4.9 million inhabitants). Methods: Longitudinal cohorts of patients born in the years 1988 to 1998 and enrolled in the VRRDR in their paediatric age were identified. Data referred to this group of patients, experiencing transition from paediatric to adult age during the years 2006–2016, are presented. Results: 2153 RD patients (44.1% females and 55.9% males) passed from childhood to adulthood in the study period, corresponding to a 3-fold increase from 2006 to 2016. The majority of these patients was affected by congenital anomalies (32.0%), by hematologic diseases (15.9%), eye disorders (12.1%) and neoplasms (7.9%). RD patients who experienced transition from paediatric age to adulthood represent the 9.2% of adult patients enrolled in the Registry at 31 December 2016. Conclusions: We described a subset of RD young adults experiencing transition into adulthood. The data reported can be considered as minimum values for estimating the size of this increasing population presenting specific transition needs. These figures are valuable for clinicians, patients and health planners. Public policy interventions are needed in order to promote dedicated care transition pathways in the broader framework of health policies devoted to RD.

Background: Estimates of rare disease (RD) population impact in terms of number of affected patients and accurate disease definition is hampered by their under-representation in current coding systems. This study tested the use of a specific RD codification system (ORPHAcodes) in five European countries/regions (Czech Republic, Malta, Romania, Spain, Veneto region-Italy) across different data sources over the period January 2019-September 2021. Results: Overall, 3133 ORPHAcodes were used to describe RD diagnoses, mainly corresponding to the disease/subtype of disease aggregation level of the Orphanet classification (82.2%). More than half of the ORPHAcodes (53.6%) described diseases having a very low prevalence (< 1 case per million), and most commonly captured rare developmental defects during embryogenesis (31.3%) and rare neurological diseases (17.6%). ORPHAcodes described disease entities more precisely than corresponding ICD-10 codes in 83.4% of cases. Conclusions: ORPHAcodes were found to be a versatile resource for the coding of RD, able to assure easiness of use and inter-country comparability across population and hospital databases. Future research on the impact of ORPHAcoding as to the impact of numbers of RD patients with improved coding in health information systems is needed to inform on the real magnitude of this public health issue.

Background: Rare diseases (RD) are a heterogeneous group of diseases, sharing aspects of complexity. Prognosis is variable, even in individuals with the same disease. Real-world data on RD as a whole are scarce. The aim of this study is to provide data on mortality and survival for a substantial group of RD deriving from a population-based registry, which covers the Veneto region in Italy (4.9 million inhabitants). Results: During the study period, 3367 deaths occurred, mainly in males (53.9%), elderly patients (63.5%) and patients with diseases having a reported prevalence of 1–9/100000 (65.6%). When standardizing by age, the mortality ratio was higher in RD patients than in the general population, SMR = 1.93 (95% CI 1.84–2.11), with an observed gender difference, 2.01 (95% CI 1.88–2.29) in females and 1.86 (95% CI 1.73–2.10) in males. The lowest survival rates are experienced by patients with rare neurologic diseases, rare skin diseases and rare systemic or rheumatologic diseases, 58%, 68% and 81%, respectively, after a 15-year observation period. It should be noted that only 18% of patients diagnosed with motor neuron diseases were alive after 15 years from diagnosis. Conclusions: Despite progress in diagnosis, treatment and care in recent years, RD patients globally have higher mortality rates and reduced survival compared to the general population, with specific variations according to gender, age and disease group.

Atypical Hemolytic Uremic Syndrome (aHUS) is a severe, systemic, rare disease (RD) that can occur in people of all ages, and is associated with high rates of morbidity and mortality. Because the management of patients with aHUS can be difficult, more effective strategies should be implemented. Faculty members from several Italian Scientific Societies, Patient Associations and Regional Institutional Experts on RDs met to discuss aHUS management within a multidisciplinary team (MDT), using a Delphi process to develop consensus recommendations. Consensus (≥70 % agreement by faculty members) was reached on 51 statements with the aim of improving patient management and outcomes. These statements provide a unified framework for the differential diagnosis of aHUS, prompt recognition of the pathology, referral to RD reference centers, selecting between treatment relapse prevention measures options, patient management by a MDT and improving the overall awareness of aHUS. Despite the broad scope of the consensus statements, several unmet needs in the management of patients with aHUS were identified, including diagnostic suspicion, rapid genetic investigations, regular review of the centers of expertise (considering the number of treated patients), permanent clinical referral in treatment centers and widespread expertise among adult and pediatric specialists. We hope that this standardized framework will form the basis of the "digital ecosystem" concept and development of possible information technology solutions to assist the MDT involved in the management of patients with aHUS.