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- Hikmat, O., et al.
(författare)
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Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases
- 2020
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 43:4, s. 726-736
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Tidskriftsartikel (refereegranskat)abstract
- Background: Variants in POLG are one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. Methods: A multinational, retrospective study using data from 155 patients with POLG variants recruited from seven European countries. Results: We describe the spectrum of clinical features associated with POLG variants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset—onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. Conclusion: Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course. © 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM
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| 2. |
- Hikmat, O., et al.
(författare)
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The impact of gender, puberty, and pregnancy in patients with POLG disease
- 2020
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 7:10, s. 2019-2025
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor.
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| 3. |
- Horn, M. A., et al.
(författare)
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Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease
- 2013
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 79:3, s. 316-320
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesX-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease. Study designAmong 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men. ResultsEighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 15% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%. ConclusionsWe found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids.
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| 6. |
- Blauhut, Veit, et al.
(författare)
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Lessons from the 2018-2019 European droughts : a collective need for unifying drought risk management
- 2022
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Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981. ; 22:6, s. 2201-2217
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Tidskriftsartikel (refereegranskat)abstract
- Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazard severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts and how the hazard is perceived by relevant stakeholders. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard, and impact. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders' perceptions of drought, impacts on water resources and beyond, water availability, and current drought management strategies on national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perception across different countries and in values of the implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study identifies an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and mitigate damage to human and natural assets.
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| 7. |
- Blauhut, Veit, et al.
(författare)
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Lessons from the 2018–2019 European droughts: A collective need for unifying drought risk management
- 2021
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Ingår i: Natural hazards and earth system sciences. - : Copernicus Publications. - 1561-8633 .- 1684-9981.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazardous severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts, and how the hazard is perceived by relevant stakeholders for inducing action. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard and impacts. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders’ perceptions of drought, impacts on water resources and beyond, water availability and current drought management strategies at national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perceptions across different countries and in values of implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study concludes with an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and lessen harm to human and natural potentials.
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