Many people living with rare disease (RD) report a difficult diagnostic process from the symptom onset until they obtain the definitive diagnosis. The aim of this study was thus to ascertain the diagnostic process in RDs, and explore the determinants related with having to wait for more than one year in this process (defined as “diagnostic delay”). We conducted a case–control study, using a purpose-designed form from the Spanish Rare Diseases Patient Registry for data-collection purposes. A descriptive analysis was performed and multivariate backward logistic regression models fitted. Based on data on 1216 patients living with RDs, we identified a series of determinants associated with experiencing diagnostic delay. These included: having to travel to see a specialist other than that usually consulted in the patient’s home province (OR 2.1; 95%CI 1.6–2.9); visiting more than 10 specialists (OR 2.6; 95%CI 1.7–4.0); being diagnosed in a region other than that of the patient’s residence at the date of symptom onset (OR 2.3; 95%CI 1.5–3.6); suffering from a RD of the nervous system (OR 1.4; 95%CI 1.0–1.8). In terms of time taken to see a specialist, waiting more than 6 months to be referred from the first medical visit was the period of time which most contributed to diagnostic delay (PAR 30.2%). In conclusion, this is the first paper to use a collaborative study based on a nationwide registry to address the diagnostic process of patients living with RDs. While the evidence shows that the diagnostic process experienced by these persons is complex, more studies are needed to determine the implications that this has for their lives and those of their families at a social, educational, occupational, psychological, and financial level.

The etiology of motor neuron disease (MND) is still unknown. The aims of this study were to: (1) analyze MND mortality at a fine-grained level; and (2) explore associations of MND and heavy metals released into Spanish river basins. MND deaths were extracted from the Spanish nationwide mortality registry (2007–2016). Standardized mortality ratios (SMRs) for MND were estimated at a municipal level. Sites that emitted quantities of heavy metals above the regulatory thresholds were obtained from the European Pollutant Release and Transfer Register database (2007–2015). The relative risks for non-exposed and exposed municipalities (considering a downstream 20 km river section) by type of heavy metal were analyzed using a log-linear model. SMRs were significantly higher in central and northern municipalities. SMRs were 1.14 (1.10–1.17) higher in areas exposed to heavy metals than in non-exposed areas: 0.95 (0.92–0.96). Considering the different metals, we found the following increased MND death risks in exposed areas: 20.9% higher risk for lead, 20.0% for zinc, 16.7% for arsenic, 15.7% for chromium, 15.4% for cadmium, 12.7% for copper, and 12.4% for mercury. This study provides associations between MND death risk and heavy metals in exposed municipalities. Further studies investigating heavy metal exposure are needed to progress in MND understanding.

Background: Huntington's disease (HD) is a progressive neurodegenerative condition characterized by chorea, dystonia, behavioral disturbances and cognitive decline. The aim of this study is to assess temporal and spatial changes on mortality attributable to HD over 30 years in Spain. Methods: HD data were extracted from the nationwide mortality registry for the period 1984-2013. Annual and 5-year gender- and age-specific rates adjusted for the standard European population were calculated. Geographic analysis was performed by districts from 1999 through 2013, and then estimated standardized mortality ratios (SMRs) and smoothed SMRs. Results: There were 1,556 HD-related deaths across the study period. An increasing trend in age-adjusted HD mortality was in evidence, specifically from 1994 through 1998. On a year-by-year basis, age-adjusted mortality rates increased from 0.076 per 100,000 population in 1984 to 0.157 in 2013. Geographical differences among districts were evident in specific areas and in the southwest of Spain with a significantly higher HD mortality risk. Conclusion: HD mortality rising trends in Spain might be attributable to improvements in diagnosis leading to a rise in prevalence. Geographical variability in HD mortality could be related to regional differences in disease prevalence, health-care disparities, or other factors which call for in-depth assessment in future studies.

Background According to the International Rare Diseases Research Consortium (IRDiRC), a known rare disease (RD) should be diagnosable within a year. This study sought: firstly, to ascertain how long it takes to obtain the diagnosis of a RD in Spain, along with its associated time trend; and secondly, to identify and measure diagnostic delay (defined by the IRDiRC as any period exceeding a year) by reference to the characteristics of RDs and the persons affected by them. Methods Using data sourced from the Spanish Rare Diseases Patient Registry, we performed a descriptive analysis of the time elapsed between symptom onset and diagnosis of each RD, by sex, age and date of symptom onset, and type of RD. We analysed the time trend across the period 1960–2021 and possible change points, using a Joinpoint regression model and assuming a Poisson distribution. The multivariate analysis was completed with backward stepwise logistic regression. Results Detailed information was obtained on 3304 persons with RDs: 56.4% had experienced delay in diagnosis of their RDs, with the mean time taken being 6.18 years (median = 2; IQR 0.2–7.5). Both the percentage of patients with diagnostic delay and the average time to diagnosis underwent a significant reduction across the study period (p < 0.001). There was a higher percentage of diagnostic delays: in women (OR 1.25; 95% CI 1.07–1.45); in cases with symptom onset at age 30–44 years (OR 1.48; 95% CI 1.19–1.84): and when analysed by type of RD, in mental and behavioural disorders (OR 4.21; 95% CI 2.26–7.85), followed by RDs of the nervous system (OR 1.39; 95% CI 1.02–1.88). Conclusions This is the first study to quantify time to diagnosis of RDs in Spain, based on data from a national registry open to any RD. Since over half of all persons affected by RDs experience delay in diagnosis, new studies are needed to ascertain the factors associated with this delay and the implications this has on the lives of patients and their families.

Official mortality statistics provide population-based data and serve to improve epidemiological knowledge of rare diseases (RDs), by helping with the description of the natural history of the disease. They are an important complement of registries and estimates of disease burden and costs. At the same time, they heighten both the visibility of these diseases and the interest in their study and the search for treatments that may increase survival. This chapter contains a European analysis of hereditary ataxia mortality, which considers the time trend in different countries and the geographical variability in risk of death. Despite the limitations of applying this data source to RDs, mortality statistics share criteria which facilitate international comparisons and are of great utility for obtaining sufficiently uniform and robust time series for analysis of low-prevalence diseases.