Patient and family experiences of lysosomal storage diseases in Canada: A qualitative interview study

Canadians born with rare diseases (RDs) experience a myriad of challenges as they navigate the healthcare system to access lifesaving drugs and related services. Canada lags behind other advanced industrialized countries in implementing a comprehensive national strategy to manage RDs and facilitate access to drugs for rare diseases (DRDs). The existing provincially managed system for accessing DRDs is fragmented, uneven, and uncoordinated. It is not reflective of patient experiences but rather aggravates patient challenges, including delayed access to treatment and inconsistent decision-making for drug coverage. The central purpose of this dissertation is to understand how lived experiences of RD patients can inform health policy and the healthcare system to improve RD care. Drawing from semi-structured interviews with RD (lysosomal storage diseases) patients and their families and a review of policy documents, this dissertation uncovers four major challenges encountered by RD patients beyond gaining access to DRDs. These include 1) difficulty in obtaining a timely correct diagnosis; 2) lack of coordinated, efficient, and holistic patient care; 3) lack of consideration of patient voice in decision-making processes; and 4) difficulty in navigating the healthcare system due to stigmatization. This dissertation also finds that the patchwork of programs that govern access to DRDs in Canadian provinces has been ineffective and has failed to support patients in receiving timely and equitable access to DRDs. The above factors demonstrate the necessity for a comprehensive national strategy for RDs that goes beyond an orphan drug framework and addresses the holistic needs of the patient population. Patients and families must be centrally included in the continuum of care and the policymaking process. Such a framework empowers people affected by RDs and reduces their marginalization and exclusion. This dissertation fills important gaps in the existing literature. It delivers important data and insights 1) by collecting extensive, hitherto unavailable, experiential data from RD patients and their families by bringing their unique voices to the policy table; 2) by making patient-centered recommendations for the proposed national RD strategy; and 3) by offering a structured patient engagement framework in the RD sector to meaningfully engage RD patients in decision-making.

BackgroundIn order to plan and improve provision of comprehensive care in Huntington’s disease (HD), it is critical to understand the gaps in healthcare and social support services provided to HD patients. Research has described utilization of healthcare services in HD in Europe, however, studies systematically examining needs for healthcare services and social support are lacking. This study aims to identify the level and type of met and unmet needs for health and social care services among patients with HD, and explore associated clinical and socio-demographic factors.MethodsEighty-six patients with a clinical diagnosis of HD living in the South-Eastern region of Norway were recruited. Socio-demographic and clinical characteristics were collected. The Needs and Provision Complexity Scale (NPCS) was used to assess the patients’ needs for healthcare and social services. Functional ability and disease stage was assessed using the UHDRS Functional assessment scales. In order to investigate factors determining the level of total unmet needs and the level of unmet needs for Health and personal care and Social care and support services, multivariate logistic regression models were used.ResultsA high level of unmet needs for health and personal care and social support services were found across all five disease stages, but most marked in disease stage III. The middle phase (disease stage III) and advanced phase (disease stages IV and V) of HD increased odds of having a high level of total unmet needs by 3.5 times and 1.4 times respectively, compared with the early phase (disease stages I and II). Similar results were found for level of unmet needs in the domain Health and personal care. Higher education tended to decrease odds of high level of unmet needs in this domain (OR = 0.48) and increase odds of higher level of unmet needs in the domain of Social care and support (OR = 1.3). Patients reporting needs on their own tended to decrease odds of having unmet needs in Health and personal care (OR = 0.57).ConclusionsNeeds for healthcare and social services in patients with HD should be assessed in a systematic manner, in order to provide adequate comprehensive care during the course of disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0324-8) contains supplementary material, which is available to authorized users.

The development of centres of expertise (CE) and European Reference Networks (ERN) in the field of rare diseases (RD) is encouraged in the Council Recommendation on an Action in the Field of RD (2009/C 151/02) (8 June 2009) and most recently in the Directive on the application of patients’ rights in cross-border healthcare (2011/24/EU) (9 March 2011) as a means of organising care for thousands of heterogeneous RD affecting scattered patient populations across Europe. The European Union Committee of Experts on Rare Diseases (EUCERD http://www.eucerd.eu) issued a set of Recommendations on Quality Criteria for Centres of Expertise for Rare Diseases in Member States [1] to guide Member States (MS) in this area. The scope of CE in terms of disease coverage is an important issue as the expectation is to provide CE for all RD patients’ needs at national level. Denmark, France, Norway, Spain and the UK, for example, have already identified existing expertise at national level and/or established centres specialised in some RD/groups of RD which have proven to be very efficient in improving quality of care. The Scientific Secretariat of the EUCERD examined the current scope of CE in countries where they exist. CE were grouped by medical area. Three or more MS have designated centres for: juvenile arthritis/ paediatric rheumatological diseases, developmental anomalies and malformations/dysmorphology, hereditary cardiac diseases, dermatological diseases, epidermolysis bullosa, pituitary diseases or hypothalamic-hypophyseal diseases, lysosomal diseases, Prader-Willi syndrome, Fabry disease, mitochondrial diseases, haemophilia/ constitutional bleeding disorders, mastocytosis, hereditary diseases of the metabolism, porphyrias, epilepsies, neuromuscular diseases, amyotrophic lateral sclerosis, pulmonary diseases, severe pulmonary hypertension, cystic fibrosis, hereditary immune deficiencies, opthalmological diseases, genetic kidney disease, cranofacial anomalies, neurofibromatosis, Rendu-Osler disease. On the basis of this experience, a consensus can be thus identified that centres are required for around 12 groups of RD, 30 subgroups, and 26 individual diseases where centres currently exist in two or more countries. Most of these groups of RD fit into the traditional organisation of healthcare by medical area. However some grouping outside of traditional medical specialities is necessary, e.g. diseases of connective tissue, rare bone diseases, neurofibromatosis, multimalformation syndromes with intellectual disability, mitochondrial diseases, lysosomal diseases, any multi-systemic complex disease, etc. This analysis could be of use for MS currently considering the organisation of CE for RD. This work was carried out by the EUCERD Scientific Secretariat with the support of EC Joint Action N°20082291.

BackgroundFucosidosis is one of the rare autosomal recessive lysosomal storage diseases (LSDs) attributed to FUCA1 variants causing the deficiency of α-L-fucosidase in vivo. Α-L-fucosidase deficiency will cause excessive accumulation of fucosylated glycoproteins and glycolipids, which eventually leads to dysfunction in all tissue systems and presents with multiple symptoms. Fucosidosis is a rare disease which is approximately 120 cases have been reported worldwide (Wang, L. et al., J Int Med Res 48, 1-6, 2020). The number of reported cases in China is no more than 10 (Zhang, X. et al., J Int Med Res 49:3000605211005975, 2021).Case presentationThe patient was an 8-year-old Chinese boy who presented with postnatal motor retardation, intellectual disability, short stature, language development retardation, coarse facial features, hepatomegaly, and diffuse angiokeratoma of both palms. His genetic testing showed the presence of a homozygous pathogenic variant (c.671delC) in the FUCA1 gene. In addition, the enzymatic activity of α-L-fucosidase was low. Ultimately, the patient was diagnosed with fucosidosis.ConclusionsFucosidosis is a rare lysosomal storage disease because of FUCA1 variants that cause the deficiency of α-L-fucosidase in vivo. An explicit diagnosis requires a combination of clinical manifestations, imaging examination, genetic testing and enzyme activity analysis. Early diagnosis plays an important role in fucosidosis.

AimTo evaluate the results of prenatal enzymatic diagnostic studies for detecting lysosomal storage diseases (LSDs) during 1992 to 2018.MethodsPregnancies subjected to “prenatal enzymatic diagnosis of LSDs” during 1992 to 2018 were retrospectively evaluated in terms of invasive prenatal tests, type of LSDs, and obstetric outcomes.ResultsA total of 142 pregnancies were evaluated for various types of LSDs of which 30, 103, and 9 cases were subjected to amniocentesis, chorionic villus sampling, and fetal blood sampling, respectively. Retrospective analysis of prenatal diagnosis revealed that LSDs affected 33% (47/142) of the fetuses. Sandhoff disease (28%), Tay‐Sachs disease (27%), and metachromatic leukodystrophy (MLD) (20%) were the most frequent LSDs among the evaluated cases with two false negatives, one each for Tay‐Sachs disease and MLD.ConclusionEnzymatic prenatal diagnoses of certain LSDs may serve as a primary intervention point for families with index cases of infantile or late infantile types of LSDs, since they are associated with poor outcomes, including mortality. In addition, enzyme studies alone may also be feasible for populations with increased risk of molecular heterogeneity, novel mutations, and low‐income settings where genetic analysis is inaccessible.

To investigate the use, challenges and opportunities associated with using patient-reported outcomes (PROs) in studies with patients with rare lysosomal storage diseases (LSDs), we conducted interviews with researchers and health technology assessment (HTA) experts, and developed the methods for a systematic review of the literature. The purpose of the review is to identify the psychometrically sound generic and disease-specific PROs used in studies with patients with five LSDs of interest: Fabry, Gaucher (Type I), Niemann-Pick (Type B) and Pompe diseases, and mucopolysaccharidosis (Types I and II). Researchers and HTA experts who responded to an email invitation participated in a telephone interview. We used qualitative content analysis to analyze the anonymized transcripts. We conducted a comprehensive literature search for studies that used PROs to investigate burden of disease or to assess the impact of interventions across the five LSDs of interest. Interviews with seven researchers and six HTA experts representing eight countries revealed five themes. These were: (i) the importance of using psychometrically sound PROs in studies with rare diseases, (ii) the paucity of disease-specific PROs, (iii) the importance of having PRO data for economic analyses, (iv) practical and psychometric limitations of existing PROs, and (v) suggestions for new PROs. The systematic review has been completed. The interviews highlight current challenges and opportunities experienced by researchers and HTA experts involved in work with rare LSDs. The ongoing systematic review will highlight the experience, opportunities, and limitations of PROs in LSDs and provide suggestions for future research.

Nonimmune hydrops fetalis (NIHF) accounts for 90% of hydrops fetalis cases. About 15% to 29% of unexplained NIHF cases are caused by lysosomal storage diseases (LSD). We review the spectrum of LSD and associated clinical findings in NIHF in a cohort of patients referred to our institution. We present a retrospective case-control study of cases with NIHF referred for LSD biochemical testing at a single center. Cases diagnosed with LSD were matched to controls with NIHF and negative LSD testing and analyzed according to the STROBE criteria to the extent the retrospective nature of this study allowed. Between January 2006 and December 2018, 28 patients with NIHF were diagnosed with a LSD. Eight types of LSD were diagnosed: galactosialidosis 8/28 (28.6%), sialic acid storage disease (SASD) 5/28 (17.9%), mucopolysaccharidosis VII 5/28 (17.9%), Gaucher 4/28 (14.3%), sialidosis 2/28 (7.1%), GM1 gangliosidosis 2/28 (7.1%), Niemann-Pick disease type C 1/28 (3.6%), and mucolipidosis II/III 1/28 (3.6%). Associated clinical features were hepatomegaly 16/21 (76.2%) vs 22/65 (33.8%), P < .05, splenomegaly 12/20 (60.0%) vs 14/58 (24.1%), P < .05, and hepatosplenomegaly 10/20 (50.0%) vs 13/58 (22.4%) P < .05. The most common LSD in NIHF were galactosialidosis, SASD, mucopolysaccharidosis VII, and Gaucher disease. LSD should be considered in unexplained NIHF cases, particularly if hepatomegaly, splenomegaly, or hepatosplenomegaly is visualized on prenatal ultrasound.

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The authors sought to create a demographic, socioeconomic, and health‐related profile of older (40+) Canadian adults with developmental disabilities (DD) residing in their communities, and to enhance current knowledge of their unmet health and social support services needs. They provide a secondary analysis of cross‐sectional data from the 2001 and 2006 Participation and Activity Limitation Surveys (PALS). The study population comprised PALS respondents who: (a) were at least 40 years of age at the time of the survey and (b) were reported having a DD. Weighted data were used to describe and compare the profiles of the study population and the comparison group (PALS respondents age 40+ with other types of disability), and to estimate the prevalence of reported unmet healthcare and social support services needs. Logistic regression analyses determined the extent to which these needs affected the target population's overall health status. The data revealed that an estimated 136,570 Canadians age 15+ reported having a DD in 2006. Of these, 66,560 (48.7%) were at least 40 years of age. An estimated 47.7% of this population rated their overall health status as either fair or poor. The prevalence of reported unmet healthcare and social services needs decreased between 2001 and 2006 for both study groups, but it was still much higher for older individuals with DD than for the comparison group in 2001 and 2006. Controlling for the effects of all the other factors, the authors found that reported unmet needs did not significantly affect respondents' overall health status. The authors concluded that compared to Canadians with other types of disability, those with DD were more likely to report unmet healthcare and social support services needs. Further research is needed to explore policies and programs which support the healthy and active aging of this population.

Rare disease (RD) patients present complex therapeutic needs. When there are therapeutic options available, orphan drugs (OD) represent only a limited proportion of prescribed treatments. This study aims at investigating the real-world use of treatments considered not replaceable and essential for the care of RD patients, besides their reimbursement status, using data from a RD population-based registry. The study is based on data derived from the Veneto region RD registry. For the period 2019-2020, we have analyzed the prescriptions of treatments defined as essential and not replaceable, besides their reimbursement status, included in therapeutic plans issued by RD expert Centres for patients resident in the Veneto region (north-east of Italy, 4.9 million inh.). The correspondent pharmaceutical costs have been estimated as well. In the study period there have been 22.186 prescriptions, included in 9,197 therapeutic plans issued for RD patients resident in the monitored area. The plans present a high level of complexity in terms of number and type of prescribed treatments, with 11% of the plans containing 5 or more prescriptions. 3,041 medicinal products have been prescribed in the study period, of whom 41% are drugs. Although these prescriptions are distributed among all the groups of RD patients, only a limited proportion of products (n=10) is responsible of the 50% of all the costs attributable to these treatments. Overall, the annual cost attributable to essential treatments not directly reimbursed by the national health system is quantifiable in 1 million euros per million inhabitants. This real-world study offers a snapshot of the complexity of treatments defined as essential, besides their reimbursement status, in therapeutic plans issued by RD expert Centres for a consistent group of RD patients monitored by a population-based registry. It highlights the complexity of the therapeutic approaches put in place for the care of RD patients, including drugs and a variety of other treatments. Population-based registries collecting data on prescribed treatments can contribute to understand the therapeutic needs of RD patients, treatments' accessibility and the impact of prescriptions on the global pharmaceutical costs.

Background: Rare diseases are a group of more than 6000 disorders that on the whole may affect 30 million European Union citizens. Most rare diseases are of genetic origin, are often chronic and life-threatening. Patients living with rare diseases typically receive care from many providers and move frequently within health care settings, so high-quality transitional care is especially important for them, as well as for their family caregivers. Poor communications, incomplete transfer of information, inadequate education of health professionals, limited access to expertise services, and the absence of a single point person to ensure continuity of care all contribute to gaps in care during transitions. The research project focuses on four rare Lysosomal storage disease - LSDs (Pompe disease, Anderson-Fabry disease, Gaucher disease and Mucopolysaccharidosis type 1) featured by the availability of treatments that allow for a good quality of life for patients and aims to gather information on the real patient journey and on the health and social services used in order to analyse and identify the key conditions for improving the care management of rare and ultra-rare diseases (RD). Methods: We conducted a national survey, distributed to patients and caregivers from the 1st of June 2016 to the 7th of August 2016. Data were gathered through questionnaires disseminated online (through the patient associations’ websites, Facebook pages and other online networks) or administered directly to patients through the patients’ associations, to maintain the privacy and anonymity. The questionnaire consisted of 70 questions related to history and pattern of referrals to specialist, time to diagnosis, core medical tests, disciplines and specialists, time and type of treatment. The questionnaire was developed based on 16 in-depth interviews to patients sampled to cover the 4 LSDs, different ages and residence at the national level and further tested through the support of patients’ associations. Data were analysed by descriptive and analytical statistics. Results: Of the survey participants, 177 patients provided evaluable data. The sample covered the national territory, was mainly composed of adult patients (average 40 age), who were diagnosed with rare LSDs 13 years ago. According to the survey patients living with rare LSD diseases visited an average of 2.4 centres before receiving an accurate diagnosis and the mean length of time from symptom onset to accurate diagnosis was around 7.3 years, however, there was a significant relationship between mean length of time for diagnosis and age (P >0.001), the mean length of time was reduced to 1.5 years for young patients (under 20 age), while was around 12 years for the older ones (over 65 age), indicating therefore the clear improvement in the diagnostic phase and in the access to reference centres. The analysis revealed the variability in tackling rarity and complexity, the wide number and specialization of professionals involved and the difficulty to provide integrated care pathways (ICPs) due to the lack of scalability and standardisation of care processes. Conclusion: The combination of rarity, complexity and lack of effective treatment creates huge obstacles to the provision of holistic care and in many cases significant medical, psychological and social needs remain unmet. Rare and ultra-rare disease challenge the most traditional care management models, indeed, people with a RD often need follow up care and support from different categories of health professionals, often from several different medical specialities, as well as by social workers and other social and local service providers which requires a level of coordination not easy to organise in most health care systems.

The Importance of Hematology Working Groups for Rare Genetic Diseases

The article describes the organization of social services provision for persons with disabilities by Territorial Social Service Centers in Ukraine. It is determined that today in Ukraine one of the most significant entities of the system of social services provision at the level of the territorial community is the Territorial Social Service Centers (Social Service Provision) (TSS), which carry out work to identify persons with disabilities among the residents of the territorial community who have found themselves in difficult living conditions and provide social services in accordance with their needs. The structure of the TSS is considered, which is determined by the needs of residents of the territorial community in social services and must have at least two departments specializing in certain types of social services. It was found that among the three main groups of social services that TSS can offer to persons with disabilities, the group of social service services is distinguished by the greatest diversity, the most common of which are social home care and day care services. It was found that social support services in most TSCOs are provided as a social service of in-kind assistance and a social service of social adaptation, and social services aimed at social prevention in disability issues are provided as information and counseling services. Since most of the services provided to persons with disabilities in TSCOs are basic, a promising direction of TSCO work has been identified as expanding their list at the expense of specialized services, in accordance with the individual needs of beneficiaries, in particular such a necessary service as a specialized comprehensive social service of temporary rest for persons caring for persons with disabilities.

The Korea Disease Control and Prevention Agency approved the “Rare Diseases Statistics in Korea” as national statistics in 2019. It published the “2019 Annual Report on Rare Disease Patients in Korea” for the first time in December 2020. It systematically collects, refines, and analyzes data related to the occurrence and treatment of rare diseases every year and provides results. Accordingly, in the “2020 Annual Report on Rare Disease Patients in Korea (2)”, detailed statistics of the year which were different from the “2020 Annual Report on Rare Disease Patients in Korea” announced in 2021 were included in the 2020 report. Therefore, the incidence, mortality, and medical service utilization of patients with rare diseases were included in the same annual report. In this report, we present the main results to promote the use of the “2020 Annual Report on Rare Disease Patients in Korea (2),” published in 2022. A total of 52,310 rare disease cases occurred among 694 diseases between January 1 and December 31, 2020, including 25,353 male (48.5%) and 26,957 female (51.5%). The death statistics referred to those who died in the same year among the cases in 2020. A total of 1,662 of 52,310 cases in 2020 died. The medical use of patients with rare diseases was calculated based on current benefit status and treatment details for the last 3 months after the registration of rare diseases in 2020. In the three months, 48,115 people were treated, and the average total cost per person was 3.1 million won. Among the treatment details, the injection, hospitalization, examination, and consultation fees were the largest in the order of payment. Since the “Annual Report on Rare Disease Patients” is written only for new patients registered for differential copayments, there are limitations, such as no information on unregistered patients. We will continue to strive to improve the “Annual Report on Rare Disease Patients” to provide more useful and accurate information.

Rare genetic disease in China: a call to improve clinical services.