Pub Date : 2024-08-14DOI: 10.1186/s13023-024-03319-2
Christine Phillips, Anne Parkinson, Tergel Namsrai, Anita Chalmers, Carolyn Dews, Dianne Gregory, Elaine Kelly, Christine Lowe, Jane Desborough
Background: People with a rare disease commonly experience long delays from the onset of symptoms to diagnosis. Rare diseases are challenging to diagnose because they are clinically heterogeneous, and many present with non-specific symptoms common to many diseases. We aimed to explore the experiences of people with myositis, primary immunodeficiency (PID), and sarcoidosis from symptom onset to diagnosis to identify factors that might impact receipt of a timely diagnosis.
Methods: This was a qualitative study using semi-structured interviews. Our approach was informed by Interpretive Phenomenological Analysis (IPA). We applied the lens of uncertainty management theory to tease out how patients experience, assess, manage and cope with puzzling and complex health-related issues while seeking a diagnosis in the cases of rare diseases.
Results: We conducted interviews with 26 people with a rare disease. Ten participants had been diagnosed with a form of myositis, 8 with a primary immunodeficiency, and 8 with sarcoidosis. Time to diagnosis ranged from 6 months to 12 years (myositis), immediate to over 20 years (PID), and 6 months to 15 years (sarcoidosis). We identified four themes that described the experiences of participants with a rare disease as they sought a diagnosis for their condition: (1) normalising and/or misattributing symptoms; (2) particularising by clinicians; (3) asserting patients' self-knowledge; and (4) working together through the diagnosable moment.
Conclusions: Managing medical uncertainty in the time before diagnosis of a rare disease can be complicated by patients discounting their own symptoms and/or clinicians discounting the scale and impact of those symptoms. Persistence on the part of both clinician and patient is necessary to reach a diagnosis of a rare disease. Strategies such as recognising pattern failure and accommodating self-labelling are key to diagnosis.
{"title":"Time to diagnosis for a rare disease: managing medical uncertainty. A qualitative study.","authors":"Christine Phillips, Anne Parkinson, Tergel Namsrai, Anita Chalmers, Carolyn Dews, Dianne Gregory, Elaine Kelly, Christine Lowe, Jane Desborough","doi":"10.1186/s13023-024-03319-2","DOIUrl":"10.1186/s13023-024-03319-2","url":null,"abstract":"<p><strong>Background: </strong>People with a rare disease commonly experience long delays from the onset of symptoms to diagnosis. Rare diseases are challenging to diagnose because they are clinically heterogeneous, and many present with non-specific symptoms common to many diseases. We aimed to explore the experiences of people with myositis, primary immunodeficiency (PID), and sarcoidosis from symptom onset to diagnosis to identify factors that might impact receipt of a timely diagnosis.</p><p><strong>Methods: </strong>This was a qualitative study using semi-structured interviews. Our approach was informed by Interpretive Phenomenological Analysis (IPA). We applied the lens of uncertainty management theory to tease out how patients experience, assess, manage and cope with puzzling and complex health-related issues while seeking a diagnosis in the cases of rare diseases.</p><p><strong>Results: </strong>We conducted interviews with 26 people with a rare disease. Ten participants had been diagnosed with a form of myositis, 8 with a primary immunodeficiency, and 8 with sarcoidosis. Time to diagnosis ranged from 6 months to 12 years (myositis), immediate to over 20 years (PID), and 6 months to 15 years (sarcoidosis). We identified four themes that described the experiences of participants with a rare disease as they sought a diagnosis for their condition: (1) normalising and/or misattributing symptoms; (2) particularising by clinicians; (3) asserting patients' self-knowledge; and (4) working together through the diagnosable moment.</p><p><strong>Conclusions: </strong>Managing medical uncertainty in the time before diagnosis of a rare disease can be complicated by patients discounting their own symptoms and/or clinicians discounting the scale and impact of those symptoms. Persistence on the part of both clinician and patient is necessary to reach a diagnosis of a rare disease. Strategies such as recognising pattern failure and accommodating self-labelling are key to diagnosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1186/s13023-024-03308-5
L Blokland, H Arponen, A Ahmad, S Colijn, H Gjørup, R John, M Li, D Mekking, S Parekh, J M Retrouvey, T Stutz Steiger, L Zhou, K Andersson
Background: Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders of varying severity characterized by bone fragility. The primary objective of this international multidisciplinary collaboration initiative was to reach a consensus for a standardized set of clinician and patient-reported outcome measures, as well as associated measuring instruments for dental care of individuals with OI, based on the aspects considered important by both experts and patients. This project is a subsequent to the Key4OI project initiated by the Care4BrittleBones foundation which aims to develop a standard set of outcome measures covering a large domain of factors affecting quality of life for people with OI. An international team of experts comprising orthodontists, pediatric dentists, oral and maxillofacial surgeons, and prosthetic dentists used a modified Delphi consensus process to select clinician-reported outcome measures (CROMs) and patient-reported outcome measures (PROMs) to evaluate oral health in individuals with OI. Important domains were identified through a literature review and by professional expertise (both CROMs and PROMs). In three focus groups of individuals with OI, important and relevant issues regarding dental health were identified. The input from the focus groups was used as the basis for the final set of outcome measures: the selected issues were attributed to relevant CROMs and, when appropriate, matched with validated questionnaires to establish the final PROMs which represented best the specific oral health-related concerns of individuals with OI.
Results: Consensus was reached on selected CROMs and PROMs for a standard set of outcome measures and measuring instruments of oral health in individuals with OI.
Conclusions: Our project resulted in consensus statements for standardization oral health PROMs and CROMs in individuals with OI. This outcome set can improve the standard of care by incorporating recommendations of professionals involved in dental care of individuals with OI. Further, it can facilitate research and international research co-operation. In addition, the significant contribution of the focus groups highlights the relevance of dental and oral health-related problems of individuals with OI.
{"title":"A standard set of outcome measures for the comprehensive assessment of oral health and occlusion in individuals with osteogenesis imperfecta.","authors":"L Blokland, H Arponen, A Ahmad, S Colijn, H Gjørup, R John, M Li, D Mekking, S Parekh, J M Retrouvey, T Stutz Steiger, L Zhou, K Andersson","doi":"10.1186/s13023-024-03308-5","DOIUrl":"10.1186/s13023-024-03308-5","url":null,"abstract":"<p><strong>Background: </strong>Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders of varying severity characterized by bone fragility. The primary objective of this international multidisciplinary collaboration initiative was to reach a consensus for a standardized set of clinician and patient-reported outcome measures, as well as associated measuring instruments for dental care of individuals with OI, based on the aspects considered important by both experts and patients. This project is a subsequent to the Key4OI project initiated by the Care4BrittleBones foundation which aims to develop a standard set of outcome measures covering a large domain of factors affecting quality of life for people with OI. An international team of experts comprising orthodontists, pediatric dentists, oral and maxillofacial surgeons, and prosthetic dentists used a modified Delphi consensus process to select clinician-reported outcome measures (CROMs) and patient-reported outcome measures (PROMs) to evaluate oral health in individuals with OI. Important domains were identified through a literature review and by professional expertise (both CROMs and PROMs). In three focus groups of individuals with OI, important and relevant issues regarding dental health were identified. The input from the focus groups was used as the basis for the final set of outcome measures: the selected issues were attributed to relevant CROMs and, when appropriate, matched with validated questionnaires to establish the final PROMs which represented best the specific oral health-related concerns of individuals with OI.</p><p><strong>Results: </strong>Consensus was reached on selected CROMs and PROMs for a standard set of outcome measures and measuring instruments of oral health in individuals with OI.</p><p><strong>Conclusions: </strong>Our project resulted in consensus statements for standardization oral health PROMs and CROMs in individuals with OI. This outcome set can improve the standard of care by incorporating recommendations of professionals involved in dental care of individuals with OI. Further, it can facilitate research and international research co-operation. In addition, the significant contribution of the focus groups highlights the relevance of dental and oral health-related problems of individuals with OI.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1186/s13023-024-03313-8
Walter E Kaufmann, Alan K Percy, Jeffrey L Neul, Jenny Downs, Helen Leonard, Paige Nues, Girish D Sharma, Theresa E Bartolotta, Gillian S Townend, Leopold M G Curfs, Orietta Mariotti, Claude Buda, Heather M O'Leary, Lindsay M Oberman, Vanessa Vogel-Farley, Katherine V Barnes, Christopher U Missling
Background: Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder associated with multiple neurologic impairments. Previous studies have shown challenges to the quality of life of individuals with RTT and their caregivers. However, instruments applied to quantify disease burden have not adequately captured the impact of these impairments on affected individuals and their families. Consequently, an international collaboration of stakeholders aimed at evaluating Burden of Illness (BOI) in RTT was organized.
Methods: Based on literature reviews and qualitative interviews with parents of children and adults with RTT, a caregiver questionnaire was constructed to evaluate 22 problems (inclusive of core characteristics, functional impairments, and comorbidities) often experienced with RTT, rated mainly with a 5-level Likert scale. The questionnaire was administered anonymously online to an international sample of 756 caregivers (predominantly parents) of girls and women with RTT. Descriptive statistics were used to identify problems of high frequency and impact on affected individuals and caregivers. Chi-square tests characterized the relationship between problem severity and impact responses, while nonparametric ANOVAs of raw and z-score adjusted scores identified agreement between severity and impact on individual and caregiver. Secondary inferential tests were used to determine the roles of age, clinical type, and country of residence on BOI in RTT.
Results: There was variability in reported frequency of problems, with the most prevalent, severe and impactful being those related to the core features of RTT (i.e., communication and fine and gross motor impairments). Chi-square analyses demonstrated interdependence between severity and impact responses, while ANOVAs showed that many problems had disproportionately greater impact than severity, either on affected individuals (e.g., hand stereotypies) or their caregivers (e.g., sleep difficulties, seizures, pain, and behavioral abnormalities). With certain exceptions (e.g., breath-holding, seizures), age, clinical type, or country of residence did not influence these BOI profiles.
Conclusions: Our data demonstrate that core features and related impairments are particularly impactful in RTT. However, problems with mild severity can also have disproportionate impact on affected individuals and, particularly, on their caregivers. Future analyses will examine the role of factors such as treatment outcomes, healthcare services, and healthcare provider's perspectives, in these BOI profiles.
{"title":"Burden of illness in Rett syndrome: initial evaluation of a disorder-specific caregiver survey.","authors":"Walter E Kaufmann, Alan K Percy, Jeffrey L Neul, Jenny Downs, Helen Leonard, Paige Nues, Girish D Sharma, Theresa E Bartolotta, Gillian S Townend, Leopold M G Curfs, Orietta Mariotti, Claude Buda, Heather M O'Leary, Lindsay M Oberman, Vanessa Vogel-Farley, Katherine V Barnes, Christopher U Missling","doi":"10.1186/s13023-024-03313-8","DOIUrl":"10.1186/s13023-024-03313-8","url":null,"abstract":"<p><strong>Background: </strong>Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder associated with multiple neurologic impairments. Previous studies have shown challenges to the quality of life of individuals with RTT and their caregivers. However, instruments applied to quantify disease burden have not adequately captured the impact of these impairments on affected individuals and their families. Consequently, an international collaboration of stakeholders aimed at evaluating Burden of Illness (BOI) in RTT was organized.</p><p><strong>Methods: </strong>Based on literature reviews and qualitative interviews with parents of children and adults with RTT, a caregiver questionnaire was constructed to evaluate 22 problems (inclusive of core characteristics, functional impairments, and comorbidities) often experienced with RTT, rated mainly with a 5-level Likert scale. The questionnaire was administered anonymously online to an international sample of 756 caregivers (predominantly parents) of girls and women with RTT. Descriptive statistics were used to identify problems of high frequency and impact on affected individuals and caregivers. Chi-square tests characterized the relationship between problem severity and impact responses, while nonparametric ANOVAs of raw and z-score adjusted scores identified agreement between severity and impact on individual and caregiver. Secondary inferential tests were used to determine the roles of age, clinical type, and country of residence on BOI in RTT.</p><p><strong>Results: </strong>There was variability in reported frequency of problems, with the most prevalent, severe and impactful being those related to the core features of RTT (i.e., communication and fine and gross motor impairments). Chi-square analyses demonstrated interdependence between severity and impact responses, while ANOVAs showed that many problems had disproportionately greater impact than severity, either on affected individuals (e.g., hand stereotypies) or their caregivers (e.g., sleep difficulties, seizures, pain, and behavioral abnormalities). With certain exceptions (e.g., breath-holding, seizures), age, clinical type, or country of residence did not influence these BOI profiles.</p><p><strong>Conclusions: </strong>Our data demonstrate that core features and related impairments are particularly impactful in RTT. However, problems with mild severity can also have disproportionate impact on affected individuals and, particularly, on their caregivers. Future analyses will examine the role of factors such as treatment outcomes, healthcare services, and healthcare provider's perspectives, in these BOI profiles.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Rare disorders comprise of ~ 7500 different conditions affecting multiple systems. Diagnosis of rare diseases is complex due to dearth of specialized medical professionals, testing labs and limited therapeutic options. There is scarcity of data on the prevalence of rare diseases in different populations. India being home to a large population comprising of 4600 population groups, of which several thousand are endogamous, is likely to have a high burden of rare diseases. The present study provides a retrospective overview of a cohort of patients with rare genetic diseases identified at a tertiary genetic test centre in India.
Results: Overall, 3294 patients with 305 rare diseases were identified in the present study cohort. These were categorized into 14 disease groups based on the major organ/ organ system affected. Highest number of rare diseases (D = 149/305, 48.9%) were identified in the neuromuscular and neurodevelopmental (NMND) group followed by inborn errors of metabolism (IEM) (D = 47/305; 15.4%). Majority patients in the present cohort (N = 1992, 61%) were diagnosed under IEM group, of which Gaucher disease constituted maximum cases (N = 224, 11.2%). Under the NMND group, Duchenne muscular dystrophy (N = 291/885, 32.9%), trinucleotide repeat expansion disorders (N = 242/885; 27.3%) and spinal muscular atrophy (N = 141/885, 15.9%) were the most common. Majority cases of β-thalassemia (N = 120/149, 80.5%) and cystic fibrosis (N = 74/75, 98.7%) under the haematological and pulmonary groups were observed, respectively. Founder variants were identified for Tay-Sachs disease and mucopolysaccharidosis IVA diseases. Recurrent variants for Gaucher disease (GBA:c.1448T > C), β-thalassemia (HBB:c.92.+5G > C), non-syndromic hearing loss (GJB2:c.71G > A), albinism (TYR:c.832 C > T), congenital adrenal hyperplasia (CYP21A2:c.29-13 C > G) and progressive pseudo rheumatoid dysplasia (CCN6:c.298T > A) were observed in the present study.
Conclusion: The present retrospective study of rare disease patients diagnosed at a tertiary genetic test centre provides first insight into the distribution of rare genetic diseases across the country. This information will likely aid in drafting future health policies, including newborn screening programs, development of target specific panel for affordable diagnosis of rare diseases and eventually build a platform for devising novel treatment strategies for rare diseases.
{"title":"Burden of rare genetic disorders in India: twenty-two years' experience of a tertiary centre.","authors":"Jayesh Sheth, Aadhira Nair, Frenny Sheth, Manali Ajagekar, Tejasvi Dhondekar, Inusha Panigrahi, Ashish Bavdekar, Sheela Nampoothiri, Chaitanya Datar, Ajit Gandhi, Mamta Muranjan, Anupriya Kaur, Manisha Desai, Mehul Mistri, Chitra Patel, Premal Naik, Maulin Shah, Koumudi Godbole, Seema Kapoor, Neerja Gupta, Sunita Bijarnia-Mahay, Sandeep Kadam, Dhaval Solanki, Soham Desai, Anand Iyer, Ketan Patel, Harsh Patel, Raju C Shah, Shalmi Mehta, Ruchi Shah, Riddhi Bhavsar, Jhanvi Shah, Mili Pandya, Bhagyadhan Patel, Sudhir Shah, Heli Shah, Shalin Shah, Shruti Bajaj, Siddharth Shah, Nilam Thaker, Umesh Kalane, Mahesh Kamate, Vykunta Raju Kn, Naresh Tayade, Sujatha Jagadeesan, Deepika Jain, Mitesh Chandarana, Jitendra Singh, Sanjiv Mehta, Beena Suresh, Harsh Sheth","doi":"10.1186/s13023-024-03300-z","DOIUrl":"10.1186/s13023-024-03300-z","url":null,"abstract":"<p><strong>Background: </strong>Rare disorders comprise of ~ 7500 different conditions affecting multiple systems. Diagnosis of rare diseases is complex due to dearth of specialized medical professionals, testing labs and limited therapeutic options. There is scarcity of data on the prevalence of rare diseases in different populations. India being home to a large population comprising of 4600 population groups, of which several thousand are endogamous, is likely to have a high burden of rare diseases. The present study provides a retrospective overview of a cohort of patients with rare genetic diseases identified at a tertiary genetic test centre in India.</p><p><strong>Results: </strong>Overall, 3294 patients with 305 rare diseases were identified in the present study cohort. These were categorized into 14 disease groups based on the major organ/ organ system affected. Highest number of rare diseases (D = 149/305, 48.9%) were identified in the neuromuscular and neurodevelopmental (NMND) group followed by inborn errors of metabolism (IEM) (D = 47/305; 15.4%). Majority patients in the present cohort (N = 1992, 61%) were diagnosed under IEM group, of which Gaucher disease constituted maximum cases (N = 224, 11.2%). Under the NMND group, Duchenne muscular dystrophy (N = 291/885, 32.9%), trinucleotide repeat expansion disorders (N = 242/885; 27.3%) and spinal muscular atrophy (N = 141/885, 15.9%) were the most common. Majority cases of β-thalassemia (N = 120/149, 80.5%) and cystic fibrosis (N = 74/75, 98.7%) under the haematological and pulmonary groups were observed, respectively. Founder variants were identified for Tay-Sachs disease and mucopolysaccharidosis IVA diseases. Recurrent variants for Gaucher disease (GBA:c.1448T > C), β-thalassemia (HBB:c.92.+5G > C), non-syndromic hearing loss (GJB2:c.71G > A), albinism (TYR:c.832 C > T), congenital adrenal hyperplasia (CYP21A2:c.29-13 C > G) and progressive pseudo rheumatoid dysplasia (CCN6:c.298T > A) were observed in the present study.</p><p><strong>Conclusion: </strong>The present retrospective study of rare disease patients diagnosed at a tertiary genetic test centre provides first insight into the distribution of rare genetic diseases across the country. This information will likely aid in drafting future health policies, including newborn screening programs, development of target specific panel for affordable diagnosis of rare diseases and eventually build a platform for devising novel treatment strategies for rare diseases.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1186/s13023-024-03203-z
Kaleigh B. Whitehall, Sarah Rose, Gillian E. Clague, Kirsten K. Ahring, Deborah A. Bilder, Cary O. Harding, Álvaro Hermida, Anita Inwood, Nicola Longo, François Maillot, Ania C. Muntau, André L. S. Pessoa, Júlio C. Rocha, Fran Rohr, Serap Sivri, Jack Said, Sheun Oshinbolu, Gillian C. Sibbring
Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that, if untreated, causes Phe accumulation in the brain leading to neurophysiologic alterations and poor outcomes. Lifelong management centers on dietary Phe restriction, yet long-term complete metabolic control is unachievable for many adults. High blood Phe levels or chronic Phe and intact protein restriction in the diet may lead to somatic comorbidities. A systematic literature review was conducted to evaluate somatic comorbidities experienced by adults with PKU. Clinical and observational studies reporting somatic comorbidities experienced by individuals with PKU aged ≥ 16 years (or classified as adults) evaluating a Phe-restricted diet with or without pharmacologic therapy versus no therapeutic intervention (including healthy controls), or pharmacologic therapy versus a Phe-restricted diet alone, were identified. PubMed® was searched (February 1, 2022 and updated November 1, 2023), using a pre-defined search strategy, followed by two-stage screening and data extraction. Included studies were grouped by PKU population comparison. 1185 records were screened; 51 studies across 12,602 individuals were extracted. Bone-related abnormalities were the most reported outcome (n = 21); several outcome measures were used. Original study groupings included: Phe-restricted diet versus healthy controls or reference values (n = 40); treatment-adherent versus those non-adherent (n = 12). Additional groups added as part of a protocol amendment included: different Phe-restricted diets (n = 4); severe versus less severe disease (n = 5). Vote counting indicated a higher burden of ≥ 1 comorbidity (or outcome measure) for the Phe-restricted diet group by 37 of 38 studies included in the analysis of Phe-restricted diet versus healthy controls; higher burden in healthy controls was reported in 12 studies. Vote counting was similar between those treatment adherent (n = 7) versus non-adherent (n = 10). Adults with PKU have a higher comorbidity burden than a non-PKU population. More robust studies are needed to better understand the relationship between effective metabolic control and comorbidity burden, using consistent outcome measures. This SLR was supported by BioMarin Pharmaceutical Inc., Novato, CA, and is registered with the Research Registry (reviewregistry1476).
{"title":"Systematic literature review of the somatic comorbidities experienced by adults with phenylketonuria","authors":"Kaleigh B. Whitehall, Sarah Rose, Gillian E. Clague, Kirsten K. Ahring, Deborah A. Bilder, Cary O. Harding, Álvaro Hermida, Anita Inwood, Nicola Longo, François Maillot, Ania C. Muntau, André L. S. Pessoa, Júlio C. Rocha, Fran Rohr, Serap Sivri, Jack Said, Sheun Oshinbolu, Gillian C. Sibbring","doi":"10.1186/s13023-024-03203-z","DOIUrl":"https://doi.org/10.1186/s13023-024-03203-z","url":null,"abstract":"Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that, if untreated, causes Phe accumulation in the brain leading to neurophysiologic alterations and poor outcomes. Lifelong management centers on dietary Phe restriction, yet long-term complete metabolic control is unachievable for many adults. High blood Phe levels or chronic Phe and intact protein restriction in the diet may lead to somatic comorbidities. A systematic literature review was conducted to evaluate somatic comorbidities experienced by adults with PKU. Clinical and observational studies reporting somatic comorbidities experienced by individuals with PKU aged ≥ 16 years (or classified as adults) evaluating a Phe-restricted diet with or without pharmacologic therapy versus no therapeutic intervention (including healthy controls), or pharmacologic therapy versus a Phe-restricted diet alone, were identified. PubMed® was searched (February 1, 2022 and updated November 1, 2023), using a pre-defined search strategy, followed by two-stage screening and data extraction. Included studies were grouped by PKU population comparison. 1185 records were screened; 51 studies across 12,602 individuals were extracted. Bone-related abnormalities were the most reported outcome (n = 21); several outcome measures were used. Original study groupings included: Phe-restricted diet versus healthy controls or reference values (n = 40); treatment-adherent versus those non-adherent (n = 12). Additional groups added as part of a protocol amendment included: different Phe-restricted diets (n = 4); severe versus less severe disease (n = 5). Vote counting indicated a higher burden of ≥ 1 comorbidity (or outcome measure) for the Phe-restricted diet group by 37 of 38 studies included in the analysis of Phe-restricted diet versus healthy controls; higher burden in healthy controls was reported in 12 studies. Vote counting was similar between those treatment adherent (n = 7) versus non-adherent (n = 10). Adults with PKU have a higher comorbidity burden than a non-PKU population. More robust studies are needed to better understand the relationship between effective metabolic control and comorbidity burden, using consistent outcome measures. This SLR was supported by BioMarin Pharmaceutical Inc., Novato, CA, and is registered with the Research Registry (reviewregistry1476).","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1186/s13023-024-03301-y
Dongye He, Mei Zhang, Yanying Li, Fupeng Liu, Bo Ban
Ankyrin repeat domain containing-protein 11 (ANKRD11), a transcriptional factor predominantly localized in the cell nucleus, plays a crucial role in the expression regulation of key genes by recruiting chromatin remodelers and interacting with specific transcriptional repressors or activators during numerous biological processes. Its pathogenic variants are strongly linked to the pathogenesis and progression of multisystem disorder known as KBG syndrome. With the widespread application of high-throughput DNA sequencing technologies in clinical medicine, numerous pathogenic variants in the ANKRD11 gene have been reported. Patients with KBG syndrome usually exhibit a broad phenotypic spectrum with a variable degree of severity, even if having identical variants. In addition to distinctive dental, craniofacial and neurodevelopmental abnormalities, patients often present with skeletal anomalies, particularly postnatal short stature. The relationship between ANKRD11 variants and short stature is not well-understood, with limited knowledge regarding its occurrence rate or underlying biological mechanism involved. This review aims to provide an updated analysis of the molecular spectrum associated with ANKRD11 variants, investigate the prevalence of the short stature among patients harboring these variants, evaluate the efficacy of recombinant human growth hormone in treating children with short stature and ANKRD11 variants, and explore the biological mechanisms underlying short stature from both scientific and clinical perspectives. Our investigation indicated that frameshift and nonsense were the most frequent types in 583 pathogenic or likely pathogenic variants identified in the ANKRD11 gene. Among the 245 KBGS patients with height data, approximately 50% displayed short stature. Most patients showed a positive response to rhGH therapy, although the number of patients receiving treatment was limited. ANKRD11 deficiency potentially disrupts longitudinal bone growth by affecting the orderly differentiation of growth plate chondrocytes. Our review offers crucial insights into the association between ANKRD11 variants and short stature and provides valuable guidance for precise clinical diagnosis and treatment of patients with KBG syndrome.
{"title":"Insights into the ANKRD11 variants and short-stature phenotype through literature review and ClinVar database search","authors":"Dongye He, Mei Zhang, Yanying Li, Fupeng Liu, Bo Ban","doi":"10.1186/s13023-024-03301-y","DOIUrl":"https://doi.org/10.1186/s13023-024-03301-y","url":null,"abstract":"Ankyrin repeat domain containing-protein 11 (ANKRD11), a transcriptional factor predominantly localized in the cell nucleus, plays a crucial role in the expression regulation of key genes by recruiting chromatin remodelers and interacting with specific transcriptional repressors or activators during numerous biological processes. Its pathogenic variants are strongly linked to the pathogenesis and progression of multisystem disorder known as KBG syndrome. With the widespread application of high-throughput DNA sequencing technologies in clinical medicine, numerous pathogenic variants in the ANKRD11 gene have been reported. Patients with KBG syndrome usually exhibit a broad phenotypic spectrum with a variable degree of severity, even if having identical variants. In addition to distinctive dental, craniofacial and neurodevelopmental abnormalities, patients often present with skeletal anomalies, particularly postnatal short stature. The relationship between ANKRD11 variants and short stature is not well-understood, with limited knowledge regarding its occurrence rate or underlying biological mechanism involved. This review aims to provide an updated analysis of the molecular spectrum associated with ANKRD11 variants, investigate the prevalence of the short stature among patients harboring these variants, evaluate the efficacy of recombinant human growth hormone in treating children with short stature and ANKRD11 variants, and explore the biological mechanisms underlying short stature from both scientific and clinical perspectives. Our investigation indicated that frameshift and nonsense were the most frequent types in 583 pathogenic or likely pathogenic variants identified in the ANKRD11 gene. Among the 245 KBGS patients with height data, approximately 50% displayed short stature. Most patients showed a positive response to rhGH therapy, although the number of patients receiving treatment was limited. ANKRD11 deficiency potentially disrupts longitudinal bone growth by affecting the orderly differentiation of growth plate chondrocytes. Our review offers crucial insights into the association between ANKRD11 variants and short stature and provides valuable guidance for precise clinical diagnosis and treatment of patients with KBG syndrome.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-10DOI: 10.1186/s13023-024-03302-x
Francesca Perego, Lorenza Chiara Zingale, Azzurra Cesoni Marcelli, Luca Ranucci, Lorenzo Rimoldi, Nurgul Nsanbayeva, Maria Rosaria Natale, Laura Adelaide Dalla Vecchia, Alessandra Gorini
Background: Hereditary Angioedema (HAE) due to C1-inhibitor deficiency (C1INH) is a rare condition, clinically characterised by recurrent swelling. The unpredictability of attacks affects the patients' quality of life (QoL). HAE patients and their families have vast unmet physical, psychological, and social needs. A human-centred design (HCD) approach to describing the needs of different user types is to utilise personas, a data-driven narrative tool for communicating user archetypes that capture the individuals' attitudes, goals, and behaviours. The aim of this study was to create and analyse personas based on HAE patients' and their caregivers' interviews. Semi-structured interviews were conducted through anthropological conversations with patients, patient-caregivers (double role of patient and caregiver), and non-affected caregivers. Qualitative and quantitative insights from analyses formed the basis to create personas.
Results: We enrolled 17 subjects: 15 patients (6 of them were patient-caregivers) and 2 non-affected caregivers. The mean age of participants was 50.3 ± 14.4 years. Eight patients were on treatment with prophylactic therapy. The mean percentage score of Angioedema Quality of Life (AE-QoL) for HAE patients was 19.8 ± 12.0. Six personas were identified describing the participants' personal history, disease management, and needs: four personas referred to patients, one to patient-caregivers, and one non-affected caregiver personas were identified. Across patient personas, the most expressed needs were psychological support and better awareness amongst healthcare professionals. Caregivers, on their side, desired better information about the disease, including the latest therapies, and higher awareness within the community.
Conclusion: A Human Centred Innovative Approach Based on Persona extends beyond the physical symptoms to encompass the psychological and social aspects of the individual's well-being also including the family in the evaluation.
{"title":"A human centred innovative approach based on persona in hereditary angioedema.","authors":"Francesca Perego, Lorenza Chiara Zingale, Azzurra Cesoni Marcelli, Luca Ranucci, Lorenzo Rimoldi, Nurgul Nsanbayeva, Maria Rosaria Natale, Laura Adelaide Dalla Vecchia, Alessandra Gorini","doi":"10.1186/s13023-024-03302-x","DOIUrl":"10.1186/s13023-024-03302-x","url":null,"abstract":"<p><strong>Background: </strong>Hereditary Angioedema (HAE) due to C1-inhibitor deficiency (C1INH) is a rare condition, clinically characterised by recurrent swelling. The unpredictability of attacks affects the patients' quality of life (QoL). HAE patients and their families have vast unmet physical, psychological, and social needs. A human-centred design (HCD) approach to describing the needs of different user types is to utilise personas, a data-driven narrative tool for communicating user archetypes that capture the individuals' attitudes, goals, and behaviours. The aim of this study was to create and analyse personas based on HAE patients' and their caregivers' interviews. Semi-structured interviews were conducted through anthropological conversations with patients, patient-caregivers (double role of patient and caregiver), and non-affected caregivers. Qualitative and quantitative insights from analyses formed the basis to create personas.</p><p><strong>Results: </strong>We enrolled 17 subjects: 15 patients (6 of them were patient-caregivers) and 2 non-affected caregivers. The mean age of participants was 50.3 ± 14.4 years. Eight patients were on treatment with prophylactic therapy. The mean percentage score of Angioedema Quality of Life (AE-QoL) for HAE patients was 19.8 ± 12.0. Six personas were identified describing the participants' personal history, disease management, and needs: four personas referred to patients, one to patient-caregivers, and one non-affected caregiver personas were identified. Across patient personas, the most expressed needs were psychological support and better awareness amongst healthcare professionals. Caregivers, on their side, desired better information about the disease, including the latest therapies, and higher awareness within the community.</p><p><strong>Conclusion: </strong>A Human Centred Innovative Approach Based on Persona extends beyond the physical symptoms to encompass the psychological and social aspects of the individual's well-being also including the family in the evaluation.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1186/s13023-024-03277-9
Leighann Litcher-Kelly, Ahmet Ozen, Sarah Ollis, Hagit Baris Feldman, Andrew Yaworsky, Paolo Medrano, Voranush Chongsrisawa, Taylor Brackin, Lorah Perlee, Marisa Walker, Sharanya Pradeep, Michael J Lenardo, Olivier A Harari, Jessica J Jalbert
Background: CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (< 100 children or young adults worldwide) and potentially fatal. The study used mixed-methods approaches to assess how pozelimab impacts the signs and symptoms of CHAPLE disease from the patient perspective by combining within-trial interviews and clinical outcome assessments (COAs) (ClinicalTrials.gov, NCT04209634).
Methods: Interviews conducted with patients/caregivers at screening and week 24 assessed the signs and symptoms of CHAPLE disease, including those which were most bothersome, and evaluated the change. Patients/caregivers and clinicians completed the COAs; interview data contextualized the meaningfulness of change.
Results: Ten patients (aged 3-19 years) were enrolled; caregivers contributed to nine interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting are the core signs and symptoms of CHAPLE disease (≥ 90% patients experienced pre-treatment); the most bothersome signs and symptoms were abdominal pain (n = 9) and facial edema (n = 1). All core signs and symptoms were reported as resolved at week 24 interviews. Severity on global assessments changed from "mild" to "very severe" at baseline to "no signs or symptoms" at week 24. Interview results were generally consistent with sign- or symptom-specific COA scores.
Conclusions: Patients with CHAPLE disease treated with pozelimab for 24 weeks experienced complete resolution of core signs and symptoms. Mixed-methods approaches can contextualize the patient experience (how patients feel and function) in rare disease trials.
Trial registration: Clinicaltrials.gov, NCT04209634, registered December 24, 2019, https://classic.
{"title":"Pozelimab for CHAPLE disease: results from in-trial interviews and clinical outcome assessments.","authors":"Leighann Litcher-Kelly, Ahmet Ozen, Sarah Ollis, Hagit Baris Feldman, Andrew Yaworsky, Paolo Medrano, Voranush Chongsrisawa, Taylor Brackin, Lorah Perlee, Marisa Walker, Sharanya Pradeep, Michael J Lenardo, Olivier A Harari, Jessica J Jalbert","doi":"10.1186/s13023-024-03277-9","DOIUrl":"10.1186/s13023-024-03277-9","url":null,"abstract":"<p><strong>Background: </strong>CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (< 100 children or young adults worldwide) and potentially fatal. The study used mixed-methods approaches to assess how pozelimab impacts the signs and symptoms of CHAPLE disease from the patient perspective by combining within-trial interviews and clinical outcome assessments (COAs) (ClinicalTrials.gov, NCT04209634).</p><p><strong>Methods: </strong>Interviews conducted with patients/caregivers at screening and week 24 assessed the signs and symptoms of CHAPLE disease, including those which were most bothersome, and evaluated the change. Patients/caregivers and clinicians completed the COAs; interview data contextualized the meaningfulness of change.</p><p><strong>Results: </strong>Ten patients (aged 3-19 years) were enrolled; caregivers contributed to nine interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting are the core signs and symptoms of CHAPLE disease (≥ 90% patients experienced pre-treatment); the most bothersome signs and symptoms were abdominal pain (n = 9) and facial edema (n = 1). All core signs and symptoms were reported as resolved at week 24 interviews. Severity on global assessments changed from \"mild\" to \"very severe\" at baseline to \"no signs or symptoms\" at week 24. Interview results were generally consistent with sign- or symptom-specific COA scores.</p><p><strong>Conclusions: </strong>Patients with CHAPLE disease treated with pozelimab for 24 weeks experienced complete resolution of core signs and symptoms. Mixed-methods approaches can contextualize the patient experience (how patients feel and function) in rare disease trials.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov, NCT04209634, registered December 24, 2019, https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT04209634 .</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1186/s13023-024-03234-6
Wladimir Mauhin, Nathalie Guffon, Marie T Vanier, Roseline Froissart, Aline Cano, Claire Douillard, Christian Lavigne, Bénédicte Héron, Nadia Belmatoug, Yurdagül Uzunhan, Didier Lacombe, Thierry Levade, Aymeric Duvivier, Ruth Pulikottil-Jacob, Fernando Laredo, Samia Pichard, Olivier Lidove
Background: Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD.
Methods: This observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan-Meier survival analyses; standardised mortality ratio (SMR) was also explored.
Results: A total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0-18.0] months (type A), 1.0 [0-3] year (type A/B), and 5.5 [0-73] years (type B). Overall, 30 patients were deceased at the study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0-3.6] year, type A/B (n = 6) was 8.5 [3.0-30.9] years, and type B (n = 10) was 57.6 [3.4-74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8-2.7] years and 11.4 [5.5-18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6-5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%).
Conclusions: This study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.
{"title":"Acid sphingomyelinase deficiency in France: a retrospective survival study.","authors":"Wladimir Mauhin, Nathalie Guffon, Marie T Vanier, Roseline Froissart, Aline Cano, Claire Douillard, Christian Lavigne, Bénédicte Héron, Nadia Belmatoug, Yurdagül Uzunhan, Didier Lacombe, Thierry Levade, Aymeric Duvivier, Ruth Pulikottil-Jacob, Fernando Laredo, Samia Pichard, Olivier Lidove","doi":"10.1186/s13023-024-03234-6","DOIUrl":"10.1186/s13023-024-03234-6","url":null,"abstract":"<p><strong>Background: </strong>Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD.</p><p><strong>Methods: </strong>This observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1<sup>st</sup> January 1990 and 31<sup>st</sup> December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan-Meier survival analyses; standardised mortality ratio (SMR) was also explored.</p><p><strong>Results: </strong>A total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0-18.0] months (type A), 1.0 [0-3] year (type A/B), and 5.5 [0-73] years (type B). Overall, 30 patients were deceased at the study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0-3.6] year, type A/B (n = 6) was 8.5 [3.0-30.9] years, and type B (n = 10) was 57.6 [3.4-74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8-2.7] years and 11.4 [5.5-18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6-5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%).</p><p><strong>Conclusions: </strong>This study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study aimed to explore the demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases.
Methods: This retrospective cross-sectional study enrolled patients diagnosed with mitochondrial diseases from the Department of Neurology at Peking University First Hospital between January 2010 and December 2021. A questionnaire covering demographic characteristics, diagnostic dilemma, treatment, economic aspects, and caregiver stress was administered, and disability was assessed using the modified Rankin Scale (mRS).
Results: A total of 183 patients (mean age: 16 (IQR: 12-25), 49.72% males) were enrolled, including 124 pediatric patients and 59 adult patients. MELAS (106. 57.92%) and Leigh syndrome (37, 20.22%) were predominant among the mitochondrial disease subtypes. Among them, 132 (72.13%) patients were initially misdiagnosed with other diseases, 58 (31.69%) patients visited 2 hospitals before confirmed as mitochondrial disease, and 39 (21.31%) patients visited 3 hospitals before confirmed as mitochondrial disease. Metabolic modifiers were the most common type of drugs used, including several dietary supplements such as L-carnitine (117, 63.93%), Coenzyme Q10 (102, 55.74%), idebenone (82, 44.81%), and vitamins (99, 54.10%) for proper mitochondrial function. Mothers are the primary caregivers for both children (36.29%) and adults (38.98%). The mRS score ranged from 0 to 5, 92.35% of the patients had different degrees of disability due to mitochondrial disease. The average monthly treatment cost was 3000 RMB for children and 3100 RMB for adults.
Conclusions: This study provided valuable insights into the characteristics and challenges of mitochondrial diseases, which underscores the need for improved awareness, diagnostic efficiency, and comprehensive support for patients and caregivers.
{"title":"Demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases: a retrospective cross-sectional study.","authors":"Xutong Zhao, Meng Yu, Wei Zhang, Yue Hou, Yun Yuan, Zhaoxia Wang","doi":"10.1186/s13023-024-03289-5","DOIUrl":"10.1186/s13023-024-03289-5","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to explore the demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases.</p><p><strong>Methods: </strong>This retrospective cross-sectional study enrolled patients diagnosed with mitochondrial diseases from the Department of Neurology at Peking University First Hospital between January 2010 and December 2021. A questionnaire covering demographic characteristics, diagnostic dilemma, treatment, economic aspects, and caregiver stress was administered, and disability was assessed using the modified Rankin Scale (mRS).</p><p><strong>Results: </strong>A total of 183 patients (mean age: 16 (IQR: 12-25), 49.72% males) were enrolled, including 124 pediatric patients and 59 adult patients. MELAS (106. 57.92%) and Leigh syndrome (37, 20.22%) were predominant among the mitochondrial disease subtypes. Among them, 132 (72.13%) patients were initially misdiagnosed with other diseases, 58 (31.69%) patients visited 2 hospitals before confirmed as mitochondrial disease, and 39 (21.31%) patients visited 3 hospitals before confirmed as mitochondrial disease. Metabolic modifiers were the most common type of drugs used, including several dietary supplements such as L-carnitine (117, 63.93%), Coenzyme Q10 (102, 55.74%), idebenone (82, 44.81%), and vitamins (99, 54.10%) for proper mitochondrial function. Mothers are the primary caregivers for both children (36.29%) and adults (38.98%). The mRS score ranged from 0 to 5, 92.35% of the patients had different degrees of disability due to mitochondrial disease. The average monthly treatment cost was 3000 RMB for children and 3100 RMB for adults.</p><p><strong>Conclusions: </strong>This study provided valuable insights into the characteristics and challenges of mitochondrial diseases, which underscores the need for improved awareness, diagnostic efficiency, and comprehensive support for patients and caregivers.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}