Epidemiology and natural history of POLG disease in Norway: a nationwide cohort study.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
07 Jun 2024
07 Jun 2024
Historique:
revised:
27
03
2024
received:
06
02
2024
accepted:
29
04
2024
medline:
7
6
2024
pubmed:
7
6
2024
entrez:
7
6
2024
Statut:
aheadofprint
Résumé
To investigate the prevalence and natural history of POLG disease in the Norwegian population. A national, population-based, retrospective study using demographic, clinical, and genetic data of patients with genetically confirmed POLG disease. The patients were diagnosed between 2002 and 2022, and were included into the Norwegian POLG Patient Registry. Patients were stratified according to age at disease onset (early <12 years, juvenile to adult 12-40 years, late ≥40 years) and resident region. Ninety-one patients were included. The point prevalence of POLG disease was 1:149,253. Birth prevalence was 1:48,780. Median age at clinical onset was 16 years (range: 2 months to 70 years). Onset occurred early in 35% (32 out of 91), juvenile-adult in 55% (50 out of 91) and late in 10% (9 out of 91). A distinct seasonal pattern in disease onset was observed, with 57% (52 out of 91) presenting between May and August. Forty-five patients (49%) had acute exacerbations that required intensive care, and this affected 72% of those in the early-onset group. The mortality rate was 54% (49 out of 91), with a median time from disease onset to death of 3 years (range: 1 month to 36 years). We provide the point prevalence and birth prevalence of POLG disease in the first nationwide study in which epidemiological and clinical data were integrated. Seasonal variations in clinical onset may offer valuable insights into disease mechanisms and modifying factors. The findings from this study are crucial for quantifying the disease burden, and contribute to evidence-based healthcare planning.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Western Norway Regional Health Authority
Organisme : Helse Vest
ID : 911944
Organisme : Oslo University Hospital
Informations de copyright
© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Saneto RP, Naviaux RK. Polymerase gamma disease through the ages. Dev Disabil Res Rev. 2010;16(2):163‐174.
Barca E, Long Y, Cooley V, et al. Mitochondrial diseases in North America: an analysis of the NAMDC registry. Neurol Genet. 2020;6(2):e402.
Nuzhnyi E, Seliverstov Y, Klyushnikov S, et al. POLG‐associated ataxias can represent a substantial part of recessive and sporadic ataxias in adults. Clin Neurol Neurosurg. 2021;201:106462.
Lipponen J, Helisalmi S, Raivo J, et al. Molecular epidemiology of hereditary ataxia in Finland. BMC Neurol. 2021;21(1):382.
Schicks J, Synofzik M, Schulte C, Schöls L. POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe. Mov Disord. 2010;25(15):2678‐2682.
Hakonen AH, Heiskanen S, Juvonen V, et al. Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet. 2005;77(3):430‐441.
Uusimaa J, Gowda V, McShane A, et al. Prospective study of POLG mutations presenting in children with intractable epilepsy: prevalence and clinical features. Epilepsia. 2013;54(6):1002‐1011.
Kollberg G, Moslemi AR, Darin N, et al. POLG1 mutations associated with progressive encephalopathy in childhood. J Neuropathol Exp Neurol. 2006;65(8):758‐768.
Piekutowska‐Abramczuk D, Kaliszewska M, Sułek A, et al. The frequency of mitochondrial polymerase gamma related disorders in a large Polish population cohort. Mitochondrion. 2019;47:179‐187.
Gorman GS, Schaefer AM, Ng Y, et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015;77(5):753‐759.
Winterthun S, Ferrari G, He L, et al. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase γ mutations. Neurology. 2005;64(7):1204‐1208.
Tan J, Wagner M, Stenton SL, et al. Lifetime risk of autosomal recessive mitochondrial disorders calculated from genetic databases. EBioMedicine. 2020;54:102730.
Van Goethem G, Dermaut B, Löfgren A, et al. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet. 2001;28(3):211‐212.
Rahman S, Copeland WC. POLG‐related disorders and their neurological manifestations. Nat Rev Neurol. 2019;15(1):40‐52.
Hikmat O, Naess K, Engvall M, et al. Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases. J Inherit Metab Dis. 2020;43(4):726‐736.
Anagnostou ME, Ng YS, Taylor RW, McFarland R. Epilepsy due to mutations in the mitochondrial polymerase gamma (POLG) gene: a clinical and molecular genetic review. Epilepsia. 2016;57(10):1531‐1545.
Hikmat O, Tzoulis C, Chong WK, et al. The clinical spectrum and natural history of early‐onset diseases due to DNA polymerase gamma mutations. Genet Med. 2017;19(11):1217‐1225.
Norway S. Population. 2023. Available from: https://www.ssb.no/befolkning/folketall/statistikk/befolkning.
Tangeraas T, Sæves I, Klingenberg C, et al. Performance of expanded newborn screening in Norway supported by post‐analytical bioinformatics tools and rapid second‐tier DNA analyses. Int J Neonatal Screen. 2020;6(3):51.
Buajitti E, Rosella LC, Zabzuni E, Young LT, Andreazza AC. Prevalence and health care costs of mitochondrial disease in Ontario, Canada: a population‐based cohort study. PLoS One. 2022;17(4):e0265744.
Cohen B, Balcells C, Hotchkiss B, Aggarwal K, Karaa A. A retrospective analysis of health care utilization for patients with mitochondrial disease in the United States: 2008‐2015. Orphanet J Rare Dis. 2018;13(1):210.
Tzoulis C, Engelsen BA, Telstad W, et al. The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases. Brain. 2006;129(Pt 7):1685‐1692.
Farnum GA, Nurminen A, Kaguni LS. Mapping 136 pathogenic mutations into functional modules in human DNA polymerase γ establishes predictive genotype‐phenotype correlations for the complete spectrum of POLG syndromes. Biochim Biophys Acta. 2014;1837(7):1113‐1121.
Nurminen A, Farnum GA, Kaguni LS. Pathogenicity in POLG syndromes: DNA polymerase gamma pathogenicity prediction server and database. BBA Clin. 2017;7:147‐156.
Hikmat O, Tzoulis C, Klingenberg C, et al. The presence of anaemia negatively influences survival in patients with POLG disease. J Inherit Metab Dis. 2017;40(6):861‐866.
Hikmat O, Naess K, Engvall M, et al. The impact of gender, puberty, and pregnancy in patients with POLG disease. Ann Clin Transl Neurol. 2020;7(10):2019‐2025.
Bindu PS, Sonam K, Chiplunkar S, et al. Mitochondrial leukoencephalopathies: a border zone between acquired and inherited white matter disorders in children? Mult Scler Relat Disord. 2018;20:84‐92.
Sofou K, De Coo IF, Isohanni P, et al. A multicenter study on Leigh syndrome: disease course and predictors of survival. Orphanet J Rare Dis. 2014;9:52.
Echaniz‐Laguna A, Chassagne M, de Sèze J, et al. POLG1 variations presenting as multiple sclerosis. Arch Neurol. 2010;67(9):1140‐1143.
Hasselmann O, Blau N, Ramaekers VT, Quadros EV, Sequeira JM, Weissert M. Cerebral folate deficiency and CNS inflammatory markers in Alpers disease. Mol Genet Metab. 2010;99(1):58‐61.
Al‐Zubeidi D, Thangarajh M, Pathak S, et al. Fatal human herpesvirus 6‐associated encephalitis in two boys with underlying POLG mitochondrial disorders. Pediatr Neurol. 2014;51(3):448‐452.
Gaudó P, Emperador S, Garrido‐Pérez N, et al. Infectious stress triggers a POLG‐related mitochondrial disease. Neurogenetics. 2020;21(1):19‐27.
Damasceno A, Von Glehn F, de Deus‐Silva L, Damasceno BP. Monthly variation of multiple sclerosis activity in the southern hemisphere: analysis from 996 relapses in Brazil. Eur J Neurol. 2012;19(4):660‐662.
Harding K, Tilling K, MacIver C, et al. Seasonal variation in multiple sclerosis relapse. J Neurol. 2017;264(6):1059‐1067.
Martynova E, Khaibullin T, Salafutdinov I, et al. Seasonal changes in serum metabolites in multiple sclerosis relapse. Int J Mol Sci. 2023;24(4):3542.