PURPOSE: This study is a cross-sectional analysis of data from the Italian registry for patients with PWS, aimed at assessing the prevalence of endocrine and metabolic abnormalities in 539 patients with Prader-Willi syndrome (PWS), aged 0.0 to 61.6 years. Demographic and genetic data were also analyzed. METHODS: Patients were recruited from 18 PWS referral centers participating in the Italian PWS registry. Each subject underwent comprehensive health screening as part of routine clinical care. RESULTS: The analysis of database revealed: (1) a reduction of obesity prevalence compared to previous data in the Italian population of PWS (51.0% versus 62.6%); (2) a high frequency of endocrine disorders (hypogonadism 53.5%, hypothyroidism 16.1%, central adrenal insufficiency 5.9%, precocious puberty 5.6%); (3) 337 individuals were undergoing GH therapy (62.5%), including 286 < 18 years (91.4%) and 51 > 18 years (22.6%); (4) a high prevalence of altered glucose metabolism (27.4%), dyslipidemia (29.7%), hyperuricemia (10.4%), hypovitaminosis D (50.2%), osteoporosis (6.9%), metabolic dysfunction-associated steatotic liver disease (33.3%) and cholelithiasis (13.3%); (5) endocrine and metabolic abnormalities were more frequent among patients > 18 years; (6) patients > 18 years had a higher rate of paternal 15q11.2-q13 deletions and a lower rate of maternal uniparental disomy for chromosome 15 than younger individuals (61.1% versus 40.9% and 31.0% versus 46.0%, respectively; p < 0.001); (7) the median age at genetic diagnosis was lower in the younger group compared to those > 18 years (0.1 years versus 3.7 years; p < 0.001). CONCLUSION: Our findings confirm the high prevalence of endocrine and metabolic comorbidities in Italian subjects with PWS.

BACKGROUND:Angelman syndrome (AS) is a rare and heterogeneous genetic disorder characterized by intellectual and psychomotor delay, speech deficits, seizures and behavioural issues. To evaluate the feasibility of collecting data by many Italian centers involved in pathology management, and to investigate the relationship between various symptoms and genotypes, a dedicated AS registry was developed. This study aims to present preliminary findings from the Italian AS registry (IReAS), with a specific focus on exploring genotype-phenotype correlations. MATERIALS AND METHODS:The IReAS, established in 2020, aims to collect information from 14 different Italian referral. It includes demography, diagnosis and genetic, patient status, therapeutic interventions and mortality data collection. RESULTS:213 patients (55.4 % female vs 44.6 % male) were included in the IReAS during the 2020-24 period. Average age at genetic diagnosis was 3.8 years; 63 % of patients was paediatric; 70.4 % of subjects had maternal deletion. Most patients exhibited global developmental delay (100 %), movement disorders (94.8 %), behavioral abnormalities (96.2 %), and a total lack of language development (95.8 %). Epilepsy is also highly prevalent (80.3 %), with a significantly higher incidence in patients with maternal deletion compared to non-deletion groups (88 % vs 61.9 %). CONCLUSIONS:The IReAS provides comprehensive data on the diagnosis, genetic subtypes and clinical features of AS patients. It can facilitate genotype-phenotype correlation analyses, offering insights into the AS natural history and potential implications for research on targeted therapies.

Spina bifida (SB) results from failure of fusion of the caudal neural tube leading to complications in several organ systems and considerable disability. The causes of this disorder are heterogeneous and multifactorial. Medical and surgical management is a lifelong necessity for people with SB (pwSB) and should be provided by a multidisciplinary team. Standardized collection of data in ad hoc registries represents an important tool to (i) collect clinical and epidemiologic data, (ii) assess the clinical management including the diagnostic delay, (iii) improve patients’ care and (iv) foster research to identify new therapeutic solutions. The present study aimed to shed light on the analyses from the first 1.000 patients included in the Italian SB registry (period 2020-23) thus boosting the contribution of registries of pathology in the improvement of knowledge and research. The Italian SB registry was established in 2020 to (i) describe the natural history of the disease, (ii) determine the clinical effectiveness of health care services, (iii) measure and monitor the quality of care of patients. It is based on a web-customizable-based system for the collection of demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality data. Clinical data are updated annually during follow-up visits. Data quality is ensured by an automatic check performed by the system enabling a constant longitudinal and vertical control of data included in the registry. Descriptive statistics, including absolute and relative frequencies, mean, standard deviation, median, and percentiles, were used to summarize the quantitative variables of interest. the Pearson’s Chi-Square Test was conducted to study the association between the qualitative variables under study. A total of 1.000 pwSB were enrolled in the first 36 months after registry establishment (period: October 2020 to October 2023) from 15 Referral paediatric and adult Italian Centres; 66,8

BACKGROUND AND AIMS:Sarcoidosis is a rare systemic granulomatous disease involving the liver in up to 20% of cases. Data on hepatic sarcoidosis (HS) prevalence and management remain limited. This study aims to provide a comprehensive analysis of HS patients across Italy, focusing on diagnostic pathways, management strategies, and prognostic factors. METHODS:This multicenter retrospective study, conducted from April 2022 to December 2023, includes data from 36 hepatology units, affiliated with the Italian Association for the Study of the Liver (AISF), invited to analyse consecutive cases of HS reported between 2003 and 2023. RESULTS:A total of 78 patients with HS were identified, with complete data available for 58 (median age 53 years; 57% female; 81% Caucasian), prospectively followed for a median of 41 months. Pulmonary and lymphatic involvement were present in 45% and 34% of cases, respectively. Isolated hepatic involvement was seen in 10%. Liver biopsy revealed granulomas in all specimens. Histological cirrhosis and clinically significant portal hypertension (CSPH) were observed in 10% and 14% of patients, respectively. Patients with CSPH had a significantly higher body mass index (BMI) compared to those without (33 vs. 25, p = 0.002). Steroids and ursodeoxycholic acid were the first-line treatments for 80% and 28% of patients, respectively, while 29% required second-line therapies. One patient died from liver-related complications. CONCLUSIONS:This nationwide study underscores the variability in HS presentation and management across Italy. Liver biopsy remains essential for diagnosis and staging. While steroids are the primary treatment, many patients require second-line therapies. Our finding of a higher BMI in patients with CSPH suggests that metabolic factors may play a role in disease progression, warranting further investigation.

Objective Central disorders of hypersomnolence, a wide and heterogeneous group of neurological disorders including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), are chronic, rare, under-recognized, and disabling conditions characterized by excessive daytime sleepiness (EDS) and other symptoms adversely impacting patients’ lives. Large, harmonized real-world datasets are needed to improve phenotypic characterization, diagnostic accuracy, and translational research. Methods The Italian Registry for Narcolepsy and Central Disorders of Hypersomnolence (ReN&IS) is a national, multicenter, observational registry established in 2022. This preliminary analysis presents and compares demographic features, disease presentation, diagnostic assessment, medical comorbidities, current treatment patterns, and symptoms’ evolution across diagnostic NT1, NT2, and IH groups of patients enrolled across 20 Italian referral centers. Results From March 2022 to September 2025, 480 cases were entered in the ReN&IS. NT1 accounted for 80.0% of cases, NT2 for 14.6%, and IH for 5.4%. NT1 showed younger age at onset and enrollment than NT2 and IH, as well as the highest burden of REM-sleep-related symptoms and clear biomarker profiles (HLA DQB1*06:02 positivity and low cerebrospinal fluid orexin-A levels). Although most patients were treated with non-pharmacological (58-77%) and pharmacological (88-94%) interventions, residual EDS was common in the different groups (65-85%). Obesity and medical comorbidities, including cardiovascular, pulmonary, and connective tissue diseases did not significantly differ across groups. Conclusions ReN&IS provides the first nationwide, real-world characterization of central disorders of hypersomnolence in Italy, highlighting diagnostic and therapeutic gaps, and offering a robust platform for future longitudinal and translational studies.

Abstract Background Prader–Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients’ care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. Materials and methods The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. Results A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019–2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. Conclusions The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.

Introduction: Studies on the epidemiology of primary sclerosing cholangitis (PSC) are mainly based on tertiary referral centers; and are retrospective case series susceptible to selection bias. The aim of this study was to estimate incidence; survival and cause of mortality of PSC in Italy; using population-based data. Methods: Data collected from the National Rare Diseases Registry (RNMR) and the National Mortality Database (NMD) were integrated and analyzed. Results: We identified 502 PSC incident cases. The crude incidence rate between 2012 and 2014 was 0.10 per 100,000 individuals. Sixty percent were male; mean age at disease onset and at diagnosis were 33 and 37 years; respectively; highlighting a mean diagnostic delay of 4 years. The rate of interregional mobility was 12%. Ten-year survival was 92%. In 32% of cases the cause of death was biliary-related; 12% died of biliary or gallbladder cancer. Conclusions: For rare diseases such as PSC; population-based cohort’s studies are of paramount importance. Incidence rates of PSC in Italy are markedly lower and survival much longer than the ones reported from tertiary; single-centre series. Moreover; the diagnostic delay and the patient interregional mobility highlights the need for increasing awareness on the disease and for resource reallocation among Italian regions within the National Health Service

Knowledge of rare diseases (RD) is often scattered among many data collections and registries of patient cohorts. Therefore, assessing the burden of RD in the general population, developing appropriate policies and planning services for the care of RD patients is difficult. This study aimed at providing a systematic picture of RD occurrence in a population as big as 60 million. Data of diagnoses were certified and collected by a network of 247 specialized centres covering the whole Italian territory. Data received (about 200,000 records) were validated according to formal criteria and, where necessary, corrected by the data sources. Data of age at onset and sex distribution are given for about 400 diseases. Incidence and/or birth prevalence are given for 275 diseases and 47 disease groups, which, altogether, comprise a substantial part of the known rare diseases. Data quality, internal consistency, and external validity of the database have also been assessed and ways to limit the impact of some discrepancies were devised. The information provided by RNMR, cutting across such a wide range of RD, represents a unique coherent basis allowing the prioritization of relevant public health measures and research activities.

Introduction: Studies on PSC are mainly based on tertiary referral, retrospective case series with relevant selection bias, and population-based epidemiologic studies are scarce.

BACKGROUND Italy has been the first country at European level to implement a population-based public health registry dedicated to rare diseases. This study describes the current situation of the Italian National Rare Diseases Registry (NRDR) and compares its data with those from the National Hospital Discharge Database (HDD). METHODS Three rare diseases were analysed: Huntington disease (HD), Hereditary Haemorragic Telangiectasia (HHT) and Prader-Willi Syndrome (PWS), selected for their different characteristics. The two sources (NRDR and HDD) were linked: incidence rate ratio (IRR), sensitivity and predictive positive value (PPV) were calculated. RESULTS Incidence rates from NRDR and from HDD were compared by age groups, and IRR calculated: 1.08 for HD, 1.41 for HHT, 1.21 for PSW. For HD, sensitivity was 0.52 and PPV 0.48; for HHT sensitivity was 0.71 and PPV 0.52; for PWS the sensitivity was 0.71 and PPV 0.58. We found a strong regional variability in the results. CONCLUSIONS The integrated use of the two sources helps tracking those cases that are not captured by the Registry; further, it is a precious tool to accurately describe clinical histories of rare disease affected individuals, in terms of concomitant pathologies and medical procedures performed during hospitalization.