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Chantal M E Tallaksen - One of the best experts on this subject based on the ideXlab platform.
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Ataxia with vitamin e deficiency in southeast norway case report
Acta Neurologica Scandinavica, 2009Co-Authors: Chantal M E Tallaksen, Jeanette Koht, Kari Anne Bjørnarå, Ellen JørumAbstract:Background - Ataxia with vitamin E deficiency (AVED) is a rare cause of Hereditary Ataxia in north European countries with unknown prevalence. Few cases are reported from these countries. Methods -Through a systematic population based study of Hereditary Ataxia in southeast Norway subjects were classified and investigated. Aims - To report a subject with Ataxia due to vitamin E deficiency in Norway. Results - One patient with AVED was identified. The subject was a 45 years old woman with progressive Ataxia from preschool age. When she was 12 years old Friedreich's Ataxia was diagnosed after neurological examination. At the age of 45 re-evaluation and re-examination was performed and genetic analysis of the Frataxin gene was negative. At that time she had truncal and extremities Ataxia, titubation of the head, pes cavus, inverted plantar response, loss of proprioceptive and vibration sense and a severe sensory neuropathy. Vitamin E in serum was undetectable and genetic analysis detected a compound heterozygous mutation, p.A120T and p.R134X, in the α-tocopherol transport protein gene on chromosome 8q13. Discussion - Vitamin E should always be assessed in progressive Ataxia of genetic or unexplained causes and especially with a Friedreich's Ataxia-like phenotype since treatment is available. Conclusion - AVED is rare in Norway, but exists, and we here report the first genetically confirmed subject with Ataxia due to vitamin E deficiency in Norway.
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prevalence of Hereditary Ataxia and spastic paraplegia in southeast norway a population based study
Brain, 2009Co-Authors: Anne Kjersti Erichsen, Asbjorg Straypedersen, Jeanette Koht, Michael Abdelnoor, Chantal M E TallaksenAbstract:A population-based, cross-sectional study was performed in southeast Norway, between January 2002 and February 2008, to identify subjects with Hereditary Ataxia and Hereditary spastic paraplegia, and to estimate the prevalence of these disorders. Patients were recruited through colleagues, families, searches in computerized hospital archives and the National Patients’ Association for Hereditary Ataxia and Spastic Paraplegia. Strict criteria were used for inclusion of familial and isolated subjects. A project neurologist examined all index subjects and clinical and genetic data were registered. The source population on January 1, 2008 was 2.63 million and the prevalence day was set as February 1, 2008. One hundred seventy-one subjects from 87 unrelated families with Hereditary Ataxia and 194 subjects from 65 unrelated families with Hereditary spastic paraplegia were included. The total prevalence was estimated at 13.9/100 000. Hereditary Ataxia prevalence in the region was estimated at 6.5/100 000: 4.2/100 000 for autosomal-dominant and 2.3/100 000 for autosomal recessive, 0.15/100 000 for Friedreich's Ataxia and 0.4/100 000 for Ataxia telangiectasia. Hereditary spastic paraplegia prevalence was 7.4/100 000: 5.5/100 000 for autosomal dominant-Hereditary spastic paraplegia, 0.6/100 000 for autosomal recessive-Hereditary spastic paraplegia and 1.3/100 000 for isolated subjects. Marked differences were found in the frequencies of Hereditary Ataxia subtypes compared with other countries, while those of the most common autosomal dominant-Hereditary spastic paraplegia genotypes, SPG4, SPG3 and SPG31, were similar to those previously reported. Clear variations between age groups and counties were observed, but no gender differences. Mean age on prevalence day was 48 years, mean age at onset was 24 years. We present the largest population study performed on Hereditary Ataxia and Hereditary spastic paraplegia prevalence and report a higher prevalence than expected. Better inclusion criteria and multiple search strategies may explain the observed differences.
Jeanette Koht - One of the best experts on this subject based on the ideXlab platform.
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Physiotherapy and Hereditary Ataxia
Norwegian Physiotherapist Association, 2018Co-Authors: Kaja Giltvedt, Hanne Ludt Fossmo, Jeanette KohtAbstract:Introduction: Hereditary Ataxia is a group of rare, progressive genetic disorders that affects the neurological system and, in particular, the cerebellum. It results in poor coordination of movement and gait. As there is no curative treatment for Hereditary Ataxia, physiotherapy is essential for maintaining function and quality of life. Main part: Hereditary Ataxia arises secondary to mutations/disease causing variants in a single gene that causes damage to the nervous system. Over 100 different genetic forms of Hereditary Ataxia have been described if all forms and syndromes are included. Research with new family cohorts continues to identify new forms every year. Patients who have been diagnosed with Hereditary Ataxia should be offered a comprehensive program of physiotherapy. Individualized assessments and therapy plans are needed because Hereditary Ataxia is a large and heterogeneous group of diseases. Such a physiotherapy plan aims to teach practical strategies to cope physically with activities of everyday life and includes the use of orthopedic and technical aids and adaptation of the environment. It also aims to maintain and improve function through a focus on balance, coordination, and strength using more specific exercises and training. It is important that the physiotherapist has in-depth knowledge about the diagnosis and collaborates effectively with doctors and other professional in order to provide the most beneficial care. Conclusion: Physiotherapy is an important component for the management of the physical effects of Hereditary Ataxia
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targeted high throughput sequencing in Hereditary Ataxia and spastic paraplegia
PLOS ONE, 2017Co-Authors: Zafar Iqbal, Jeanette Koht, Siri L Rydning, Iselin Marie Wedding, Lasse Pihlstrom, Aina RengmarkAbstract:Hereditary Ataxia and spastic paraplegia are heterogeneous monogenic neurodegenerative disorders. To date, a large number of individuals with such disorders remain undiagnosed. Here, we have assessed molecular diagnosis by gene panel sequencing in 105 early and late-onset Hereditary Ataxia and spastic paraplegia probands, in whom extensive previous investigations had failed to identify the genetic cause of disease. Pathogenic and likely-pathogenic variants were identified in 20 probands (19%) and variants of uncertain significance in ten probands (10%). Together these accounted for 30 probands (29%) and involved 18 different genes. Among several interesting findings, dominantly inherited KIF1A variants, p.(Val8Met) and p.(Ile27Thr) segregated in two independent families, both presenting with a pure spastic paraplegia phenotype. Two homozygous missense variants, p.(Gly4230Ser) and p.(Leu4221Val) were found in SACS in one consanguineous family, presenting with spastic Ataxia and isolated cerebellar atrophy. The average disease duration in probands with pathogenic and likely-pathogenic variants was 31 years, ranging from 4 to 51 years. In conclusion, this study confirmed and expanded the clinical phenotypes associated with known disease genes. The results demonstrate that gene panel sequencing and similar sequencing approaches can serve as efficient diagnostic tools for different heterogeneous disorders. Early use of such strategies may help to reduce both costs and time of the diagnostic process.
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Ataxia with vitamin e deficiency in southeast norway case report
Acta Neurologica Scandinavica, 2009Co-Authors: Chantal M E Tallaksen, Jeanette Koht, Kari Anne Bjørnarå, Ellen JørumAbstract:Background - Ataxia with vitamin E deficiency (AVED) is a rare cause of Hereditary Ataxia in north European countries with unknown prevalence. Few cases are reported from these countries. Methods -Through a systematic population based study of Hereditary Ataxia in southeast Norway subjects were classified and investigated. Aims - To report a subject with Ataxia due to vitamin E deficiency in Norway. Results - One patient with AVED was identified. The subject was a 45 years old woman with progressive Ataxia from preschool age. When she was 12 years old Friedreich's Ataxia was diagnosed after neurological examination. At the age of 45 re-evaluation and re-examination was performed and genetic analysis of the Frataxin gene was negative. At that time she had truncal and extremities Ataxia, titubation of the head, pes cavus, inverted plantar response, loss of proprioceptive and vibration sense and a severe sensory neuropathy. Vitamin E in serum was undetectable and genetic analysis detected a compound heterozygous mutation, p.A120T and p.R134X, in the α-tocopherol transport protein gene on chromosome 8q13. Discussion - Vitamin E should always be assessed in progressive Ataxia of genetic or unexplained causes and especially with a Friedreich's Ataxia-like phenotype since treatment is available. Conclusion - AVED is rare in Norway, but exists, and we here report the first genetically confirmed subject with Ataxia due to vitamin E deficiency in Norway.
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prevalence of Hereditary Ataxia and spastic paraplegia in southeast norway a population based study
Brain, 2009Co-Authors: Anne Kjersti Erichsen, Asbjorg Straypedersen, Jeanette Koht, Michael Abdelnoor, Chantal M E TallaksenAbstract:A population-based, cross-sectional study was performed in southeast Norway, between January 2002 and February 2008, to identify subjects with Hereditary Ataxia and Hereditary spastic paraplegia, and to estimate the prevalence of these disorders. Patients were recruited through colleagues, families, searches in computerized hospital archives and the National Patients’ Association for Hereditary Ataxia and Spastic Paraplegia. Strict criteria were used for inclusion of familial and isolated subjects. A project neurologist examined all index subjects and clinical and genetic data were registered. The source population on January 1, 2008 was 2.63 million and the prevalence day was set as February 1, 2008. One hundred seventy-one subjects from 87 unrelated families with Hereditary Ataxia and 194 subjects from 65 unrelated families with Hereditary spastic paraplegia were included. The total prevalence was estimated at 13.9/100 000. Hereditary Ataxia prevalence in the region was estimated at 6.5/100 000: 4.2/100 000 for autosomal-dominant and 2.3/100 000 for autosomal recessive, 0.15/100 000 for Friedreich's Ataxia and 0.4/100 000 for Ataxia telangiectasia. Hereditary spastic paraplegia prevalence was 7.4/100 000: 5.5/100 000 for autosomal dominant-Hereditary spastic paraplegia, 0.6/100 000 for autosomal recessive-Hereditary spastic paraplegia and 1.3/100 000 for isolated subjects. Marked differences were found in the frequencies of Hereditary Ataxia subtypes compared with other countries, while those of the most common autosomal dominant-Hereditary spastic paraplegia genotypes, SPG4, SPG3 and SPG31, were similar to those previously reported. Clear variations between age groups and counties were observed, but no gender differences. Mean age on prevalence day was 48 years, mean age at onset was 24 years. We present the largest population study performed on Hereditary Ataxia and Hereditary spastic paraplegia prevalence and report a higher prevalence than expected. Better inclusion criteria and multiple search strategies may explain the observed differences.
Clementina Mesaros - One of the best experts on this subject based on the ideXlab platform.
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low apolipoprotein a i levels in friedreich s Ataxia and in frataxin deficient cells implications for therapy
PLOS ONE, 2018Co-Authors: Qingqing Wang, Lili Guo, Cassandra Strawser, Lauren Hauser, Weiting Hwang, Nathaniel W Snyder, David A Lynch, Clementina MesarosAbstract:Friedreich’s Ataxia (FA) is an autosomal recessive neurodegenerative disorder, which results primarily from reduced expression of the mitochondrial protein frataxin. FA has an estimated prevalence of one in 50,000 in the population, making it the most common Hereditary Ataxia. Paradoxically, mortality arises most frequently from cardiomyopathy and cardiac failure rather than from neurological effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of mortality from cardiomyopathy and heart failure. However, the pathophysiology of heart disease in FA is non-vascular and there are conflicting data on HDL-cholesterol in FA. Two studies have shown a decrease in HDL-cholesterol compared with controls and two have shown there was no difference between FA and controls. One also showed that there was no difference in serum Apo-A-I levels in FA when compared with controls. Using a highly specific stable isotope dilution mass spectrometry-based assay, we demonstrated a 21.6% decrease in serum ApoA-I in FA patients (134.8 mg/dL, n = 95) compared with non-affected controls (172.1 mg/dL, n = 95). This is similar to the difference in serum ApoA-I levels between non-smokers and tobacco smokers. Knockdown of frataxin by > 70% in human hepatoma HepG2 cells caused a 20% reduction in secreted ApoA-I. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor caused a 200% increase in HMG-CoA in the control HepG2 cells with a similar increase in the frataxin knockdown HepG2 cells, back to levels found in the control cells. There was a concomitant 20% increase in secreted ApoA-I to levels found in the control cells that were treated with simvastatin. This study provides compelling evidence that ApoA-I levels are reduced in FA patients compared with controls and suggest that statin treatment would normalize the ApoA-I levels.
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Low apolipoprotein A-I levels in Friedreich’s Ataxia and in frataxin-deficient cells: Implications for therapy
2018Co-Authors: Qingqing Wang, Lili Guo, Cassandra Strawser, Weiting Hwang, Nathaniel W Snyder, Clementina Mesaros, Lauren A. Hauser, David R. Lynch, Ian A. BlairAbstract:Friedreich’s Ataxia (FA) is an autosomal recessive neurodegenerative disorder, which results primarily from reduced expression of the mitochondrial protein frataxin. FA has an estimated prevalence of one in 50,000 in the population, making it the most common Hereditary Ataxia. Paradoxically, mortality arises most frequently from cardiomyopathy and cardiac failure rather than from neurological effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of mortality from cardiomyopathy and heart failure. However, the pathophysiology of heart disease in FA is non-vascular and there are conflicting data on HDL-cholesterol in FA. Two studies have shown a decrease in HDL-cholesterol compared with controls and two have shown there was no difference between FA and controls. One also showed that there was no difference in serum Apo-A-I levels in FA when compared with controls. Using a highly specific stable isotope dilution mass spectrometry-based assay, we demonstrated a 21.6% decrease in serum ApoA-I in FA patients (134.8 mg/dL, n = 95) compared with non-affected controls (172.1 mg/dL, n = 95). This is similar to the difference in serum ApoA-I levels between non-smokers and tobacco smokers. Knockdown of frataxin by > 70% in human hepatoma HepG2 cells caused a 20% reduction in secreted ApoA-I. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor caused a 200% increase in HMG-CoA in the control HepG2 cells with a similar increase in the frataxin knockdown HepG2 cells, back to levels found in the control cells. There was a concomitant 20% increase in secreted ApoA-I to levels found in the control cells that were treated with simvastatin. This study provides compelling evidence that ApoA-I levels are reduced in FA patients compared with controls and suggest that statin treatment would normalize the ApoA-I levels.
Paula Coutinho - One of the best experts on this subject based on the ideXlab platform.
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the global epidemiology of Hereditary Ataxia and spastic paraplegia a systematic review of prevalence studies
Neuroepidemiology, 2014Co-Authors: Luis Ruano, Claudia Raquel Ferrao De Melo, Carolina M Silva, Paula CoutinhoAbstract:Background: Hereditary cerebellar Ataxias (HCA) and Hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with p
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Hereditary Ataxia and spastic paraplegia in portugal a population based prevalence study
JAMA Neurology, 2013Co-Authors: Paula Coutinho, Luis Ruano, Jose L Loureiro, Vitor Tedim Cruz, Jose Barros, Assuncao Tuna, Clara Barbot, Joao Tiago Guimaraes, Isabel Alonso, Isabel SilveiraAbstract:Importance Epidemiological data on Hereditary cerebellar Ataxia (HCA) and Hereditary spastic paraplegia (HSP) are scarce. Objective To present the prevalence and distribution of HCA and HSP in Portugal. Design and Setting Population-based, nationwide, systematic survey, from January 1, 1994, through April 15, 2004, in Portugal. Participants Multiple sources of information were used (review of clinical files, active collaboration of neurologists and geneticists, and investigation of affected families), but the main source was active collaboration of general practitioners. Patients were examined by the same team of neurologists, using homogeneous inclusion criteria. The clinical data were registered, and all families were genetically tested. Results Overall, 1336 patients from a population of 10 322 million were diagnosed as having HCA or HSP, a prevalence of 12.9 per 100 000 population. Hereditary cerebellar Ataxia was more prevalent (prevalence, 8.9 per 100 000 population; 5.6 for dominant and 3.3 for recessive Ataxias) than HSP (prevalence, 4.1 per 100 000 population; 2.4 for dominant and 1.6 for recessive). Machado-Joseph disease (spinocerebellar Ataxia type 3) (prevalence, 3.1 per 100 000 population), Friedreich Ataxia (prevalence, 1.0 per 100 000 population), and Ataxia with oculomotor apraxia (prevalence, 0.4 per 100 000 population) were the most frequent HCAs. Spastic paraplegia types 4 (prevalence, 0.91 per 100 000 population), 3 (prevalence, 0.14 per 100 000 population), and 11 (prevalence, 0.26 per 100 000 population) were the most prevalent HSPs. Conclusions and Relevance This population-based survey covered all the Portuguese territory and mobilized most general practitioners and health centers. To our best knowledge, this survey was the largest ever performed for HCA and HSP. Prevalence of autosomal dominant Ataxias was high, particularly for Machado-Joseph disease (spinocerebellar Ataxia type 3). The genetic cause has not been identified in 39.7% of the patients studied.
Sara Perezluz - One of the best experts on this subject based on the ideXlab platform.
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altered secretome and ros production in olfactory mucosa stem cells derived from friedreich s Ataxia patients
International Journal of Molecular Sciences, 2020Co-Authors: Sara Perezluz, Frida Loria, Yurika Katsujimenez, Daniel Oberdoerfer, Oscarli Yang, Filip Lim, Jose Luis Munozblanco, Javier DiaznidoAbstract:Friedreich's Ataxia is the most common Hereditary Ataxia for which there is no cure or approved treatment at present. However, therapeutic developments based on the understanding of pathological mechanisms underlying the disease have advanced considerably, with the implementation of cellular models that mimic the disease playing a crucial role. Human olfactory ecto-mesenchymal stem cells represent a novel model that could prove useful due to their accessibility and neurogenic capacity. Here, we isolated and cultured these stem cells from Friedreich´s Ataxia patients and healthy donors, characterizing their phenotype and describing disease-specific features such as reduced cell viability, impaired aconitase activity, increased ROS production and the release of cytokines involved in neuroinflammation. Importantly, we observed a positive effect on patient-derived cells, when frataxin levels were restored, confirming the utility of this in vitro model to study the disease. This model will improve our understanding of Friedreich´s Ataxia pathogenesis and will help in developing rationally designed therapeutic strategies.