999 results match your criteria Refsum Disease

How the brain fights fatty acids' toxicity.

Neurochem Int 2021 May 1;148:105050. Epub 2021 May 1.

Institut für Inflammation und Neurodegeneration (Neurobiochemie), Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Leipziger Straße 44, D-39120, Magdeburg, Germany. Electronic address:

Neurons spurn hydrogen-rich fatty acids for energizing oxidative ATP synthesis, contrary to other cells. This feature has been mainly attributed to a lower yield of ATP per reduced oxygen, as compared to glucose. Moreover, the use of fatty acids as hydrogen donor is accompanied by severe β-oxidation-associated ROS generation. Read More

View Article and Full-Text PDF

Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment.

J Alzheimers Dis 2021 ;81(3):1211-1229

Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Poznań, Poland.

Background: Identification of modifiable risk factors that affect cognitive decline is important for the development of preventive and treatment strategies. Status of paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme, may play a role in the development of neurological diseases, including Alzheimer's disease.

Objective: We tested a hypothesis that PON1 status predicts cognition in individuals with mild cognitive impairment (MCI). Read More

View Article and Full-Text PDF
January 2021

Anti--homocysteine-protein autoantibodies are associated with impaired cognition.

Alzheimers Dement (N Y) 2021 31;7(1):e12159. Epub 2021 Mar 31.

Department of Biochemistry and Biotechnology Poznań University of Life Sciences Poznań Poland.

Introduction: Elevated homocysteine (Hcy) and related metabolites accelerate Alzheimer's disease. Hcy-lowering B vitamins slow brain atrophy/cognitive decline in mild cognitive impairment (MCI). Modification with Hcy-thiolactone generates auto-immunogenic -Hcy-protein. Read More

View Article and Full-Text PDF

Homocysteine - from disease biomarker to disease prevention.

A D Smith H Refsum

J Intern Med 2021 Mar 3. Epub 2021 Mar 3.

From the, University Department of Pharmacology, Oxford, UK.

We have reviewed the literature and have identified more than 100 diseases or conditions that are associated with raised concentrations of plasma total homocysteine. The commonest associations are with cardiovascular diseases and diseases of the central nervous system, but a large number of developmental and age-related conditions are also associated. Few other disease biomarkers have so many associations. Read More

View Article and Full-Text PDF

Twins with PEX7 related intellectual disability and cataract: Highlighting phenotypes of peroxisome biogenesis disorder 9B.

Am J Med Genet A 2021 05 14;185(5):1504-1508. Epub 2021 Feb 14.

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Peroxisome biogenesis disorders (PBDs) are a group of autosomal recessive disorders caused due to impaired peroxisome assembly affecting the formation of functional peroxisomes. PBDs are caused by a mutation in PEX gene family resulting in disease manifestation with extreme variability ranging from the onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults. Disease causing variations in PEX7 is known to cause severe rhizomelic chondrodysplasia punctata type 1 and PBD 9B, an allelic disorder resulting in a milder phenotype, often indistinguishable from that of classic Refsum disease. Read More

View Article and Full-Text PDF

Plasma Sulfur Amino Acids and Risk of Cerebrovascular Diseases: A Nested Case-Control Study in the EPIC-Norfolk Cohort.

Stroke 2021 01 22;52(1):172-180. Epub 2020 Dec 22.

Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, United Kingdom (N.J.W., N.G.F., F.I.).

Background And Purpose: B-vitamin supplements lower circulating concentrations of homocysteine and may reduce stroke incidence. Homocysteine concentrations are associated with the incidence of stroke but other sulfur-containing compounds in the related metabolic pathway have not yet been investigated for an association with incident cerebrovascular diseases.

Methods: Nested within the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk cohort, we established a case-control study with 480 incident cases of cerebrovascular diseases and 480 controls matched by age, sex, and year of baseline examination (1993-1997). Read More

View Article and Full-Text PDF
January 2021

Genome sequencing identifies a rare case of moderate Zellweger spectrum disorder caused by a defect: Case report and literature review.

Mol Genet Metab Rep 2020 Dec 19;25:100664. Epub 2020 Oct 19.

Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.

Defects in are associated with a severe neonatal-lethal form of Zellweger spectrum disorder. We report two moderately affected siblings whose clinical and biochemical phenotypes expand the reported spectrum of -related disease. Genome sequencing of an adolescent male with progressive movement disorder, spasticity and neurodegeneration, and previous non-diagnostic plasma very-long chain fatty acid analysis, revealed a homozygous likely pathogenic missense variant in [c. Read More

View Article and Full-Text PDF
December 2020

Improved electroretinographic responses following dietary intervention in a patient with Refsum disease.

JIMD Rep 2020 Sep 12;55(1):32-37. Epub 2020 Jul 12.

Department of Medical Genetics University of Alberta Edmonton Alberta Canada.

Refsum disease is a rare inherited metabolic disorder arising from a defect in peroxisomal metabolism. Patients lack the functional enzyme phytanoyl-CoA hydroxylase, resulting in perturbed alpha oxidation of fatty acids. Phytanic acid accumulates in nervous and adipose tissue and leads to several disease phenotypes including early-onset retinal degeneration, hearing loss, peripheral neuropathy, anosmia, and cerebellar ataxia, among others. Read More

View Article and Full-Text PDF
September 2020

Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome'.

J Neuromuscul Dis 2021 ;8(3):383-400

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Background: Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.

Objective: We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies. Read More

View Article and Full-Text PDF
January 2021

Association of Homocysteine, Methionine, and MTHFR 677C>T Polymorphism With Rate of Cardiovascular Multimorbidity Development in Older Adults in Sweden.

JAMA Netw Open 2020 05 1;3(5):e205316. Epub 2020 May 1.

Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Sweden.

Importance: Strong evidence links high total serum homocysteine (tHcy) and low methionine (Met) levels with higher risk of ischemic disease, but other cardiovascular (CV) diseases may also be associated with their pleiotropic effects.

Objectives: To investigate the association of serum concentrations of tHcy and Met with the rate of CV multimorbidity development in older adults and to explore the role of methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism in this association.

Design, Setting, And Participants: The Swedish National Study on Aging and Care in Kungsholmen is a cohort study of randomly selected individuals aged 60 years or older. Read More

View Article and Full-Text PDF

Laparoscopy-assisted versus balloon enteroscopy-assisted ERCP after Roux-en-Y gastric bypass.

Endoscopy 2020 08 21;52(8):654-661. Epub 2020 Apr 21.

Clinical Effectiveness Research Group, Department of Health Management and Health Economics, University of Oslo, Oslo, Norway.

Background: Patients who have undergone Roux-en-Y gastric bypass (RYGB) are at increased risk of biliary disease necessitating endoscopic retrograde cholangiopancreatography (ERCP). The most widely used approaches to perform ERCP after RYGB are laparoscopy-assisted ERCP (LA-ERCP) and balloon enteroscopy-assisted ERCP (BEA-ERCP). There are few studies comparing these procedures. Read More

View Article and Full-Text PDF

Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease.

FEBS J 2020 12 31;287(23):5096-5113. Epub 2020 Mar 31.

Systems Medicine of Metabolism and Signalling, Laboratory of Paediatrics, University of Groningen, University Medical Centre Groningen, The Netherlands.

Refsum disease (RD) is an inborn error of metabolism that is characterised by a defect in peroxisomal α-oxidation of the branched-chain fatty acid phytanic acid. The disorder presents with late-onset progressive retinitis pigmentosa and polyneuropathy and can be diagnosed biochemically by elevated levels of phytanate in plasma and tissues of patients. To date, no cure exists for RD, but phytanate levels in patients can be reduced by plasmapheresis and a strict diet. Read More

View Article and Full-Text PDF
December 2020

Body mass index determines the response of plasma sulfur amino acids to methionine loading.

Biochimie 2020 Jun 5;173:107-113. Epub 2020 Mar 5.

Department of Pharmacology, University of Oxford, Oxford, UK; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Evidence from human, animal and cellular studies suggests that high plasma total cysteine (tCys) is causally linked to human obesity, but determinants of population tCys variability are unknown. We hypothesized that tCys elevation in obesity may be mediated by an altered tCys response to intake of its precursor, methionine. We investigated whether BMI influences the change in plasma tCys, total homocysteine (tHcy) and total cysteinylglycine (tCysGly) 6h following a 100 mg/kg oral methionine load in 800 healthy subjects and 750 cardiovascular disease (CVD) cases. Read More

View Article and Full-Text PDF

Genotype-phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome.

J Peripher Nerv Syst 2020 06 24;25(2):112-116. Epub 2020 Feb 24.

Department of Neurology, University Hospital Essen, Essen, Germany.

PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot-Marie-Tooth disease and Refsum disease. We describe the genotype-phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome. Read More

View Article and Full-Text PDF

Use of electron microscopy when screening liver biopsies from neonates and infants: experience from a single tertiary children's hospital (1991-2017).

Ultrastruct Pathol 2020 Jan 3;44(1):32-41. Epub 2020 Jan 3.

Genetics Division, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

: Although the role of electron microscopy is diminishing in several areas of adult pathology, it remains an essential tool for the study of pediatric liver biopsies.: Clinical charts, histologic slides and EM materials of native liver biopsies from patients <1 year old (1991-2017) were reviewed.: 677 biopsies were performed on 353 males and 324 females. Read More

View Article and Full-Text PDF
January 2020

Adult onset seizures in learning disability.

J R Coll Physicians Edinb 2019 Dec;49(4):309-310

Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Lower Lane, Liverpool L9 7LJ, UK,

View Article and Full-Text PDF
December 2019

[Screening for ocular involvement in deaf children].

Pan Afr Med J 2019 5;33:174. Epub 2019 Jul 5.

Service d'Ophtalmologie, CHU Mohammed VI, Marrakech, Maroc.

The association between deafness and visual disorders is frequent. These disorders range from simple refractive disorder to severe disease that can lead to disability. Hence the interest of early screening. Read More

View Article and Full-Text PDF
October 2019

Creatinine, total cysteine and uric acid are associated with serum retinol in patients with cardiovascular disease.

Eur J Nutr 2020 Sep 9;59(6):2383-2393. Epub 2019 Sep 9.

Centre for Nutrition, Department of Clinical Science, University of Bergen, Haukelandsbakken, 5009, Bergen, Norway.

Purpose: We hypothesized that biomarkers and dietary factors related to cardiovascular disease risk were associated with serum retinol and evaluated these potential associations in patients with suspected coronary artery disease (CAD).

Methods: We used cross-sectional data from 4116 patients hospitalised for suspected CAD. Dietary data were obtained from a subgroup of 1962 patients using a food frequency questionnaire. Read More

View Article and Full-Text PDF
September 2020

Association of Methionine to Homocysteine Status With Brain Magnetic Resonance Imaging Measures and Risk of Dementia.

JAMA Psychiatry 2019 11;76(11):1198-1205

Aging Research Center, Karolinska Institute, Stockholm, Sweden.

Importance: Impairment of methylation status (ie, methionine to homocysteine ratio) may be a modifiable risk factor for structural brain changes and incident dementia.

Objective: To investigate the association of serum markers of methylation status and sulfur amino acids with risk of incident dementia, Alzheimer disease (AD), and the rate of total brain tissue volume loss during 6 years.

Design, Setting, And Participants: This population-based longitudinal study was performed from March 21, 2001, to October 10, 2010, in a sample of 2570 individuals aged 60 to 102 years from the Swedish Study on Aging and Care in Kungsholmen who were dementia free at baseline and underwent comprehensive examinations and structural brain magnetic resonance imaging (MRI) on 2 to 3 occasions during 6 years. Read More

View Article and Full-Text PDF
November 2019

Pregnancy outcome in Refsum disease: Affected fetuses and children born to an affected mother.

JIMD Rep 2019 Mar 14;46(1):11-15. Epub 2019 Mar 14.

Laboratoire de Biochimie Métabolique Centre de Référence en Maladies Héréditaires du Métabolisme, Institut Fédératif de Biologie, CHU de Toulouse Toulouse France.

We describe the case of a young woman, from a consanguineous family, affected by adult Refsum disease (ARD, OMIM#266500). ARD is a rare peroxisomal autosomal recessive disease due to deficient alpha-oxidation of phytanic acid (PA), a branched-chain fatty acid. The accumulation of PA in organs is thought to be responsible for disease symptoms. Read More

View Article and Full-Text PDF

Glutathione Serum Levels and Rate of Multimorbidity Development in Older Adults.

J Gerontol A Biol Sci Med Sci 2020 05;75(6):1089-1094

Aging Research Center, NVS Department, Karolinska Institutet, Stockholm University, Sweden.

We aimed to investigate the association between baseline levels of total serum glutathione (tGSH) and rate of chronic disease accumulation over time. The study population (n = 2,596) was derived from a population-based longitudinal study on ≥60-year-olds living in Stockholm. Participants were clinically assessed at baseline, 3- and 6-year follow-ups. Read More

View Article and Full-Text PDF

Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease: The OmegAD Study.

J Alzheimers Dis 2019 ;69(1):189-197

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

Background: Trials of supplementation with omega-3 fatty acids (ω3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and ω3-FAs in relation to brain atrophy and cognitive decline.

Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of ω3-FAs supplementation on cognitive performance in moderate AD. Read More

View Article and Full-Text PDF
September 2020

The kynurenine pathway and cognitive performance in community-dwelling older adults. The Hordaland Health Study.

Brain Behav Immun 2019 01 25;75:155-162. Epub 2018 Oct 25.

Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Institute of Clinical Science, University of Bergen, Norway.

Introduction: Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults.

Methods: This cross-sectional study included 2174 participants aged 70-72 years of the community-based Hordaland Health Study. Read More

View Article and Full-Text PDF
January 2019

Inborn Errors of Metabolism: Refsum Disease.

Adv Exp Med Biol 2018;1085:191-192

Department of Ophthalmology, Columbia University, Edward S. Harkness Eye Institute, NewYork-Presbyterian Hospital, New York, NY, USA.

Patient with Refsum disease present with nyctalopia, and the fundus shows progressive panretinal degeneration. Vision gradually decreases, with progressive peripheral constriction. The pupil usually does not dilate well. Read More

View Article and Full-Text PDF

Peroxisomes and Their Central Role in Metabolic Interaction Networks in Humans.

Subcell Biochem 2018;89:345-365

Laboratory Genetic Metabolic Diseases, Departments Clinical Chemistry and Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Peroxisomes catalyze a number of essential metabolic functions and impairments in any of these are usually associated with major clinical signs and symptoms. In contrast to mitochondria which are autonomous organelles that can catalyze the degradation of fatty acids, certain amino acids and other compounds all by themselves, peroxisomes are non-autonomous organelles which are highly dependent on the interaction with other organelles and compartments to fulfill their role in metabolism. This includes mitochondria, the endoplasmic reticulum, lysosomes, and the cytosol. Read More

View Article and Full-Text PDF

Application of machine learning algorithms for the differential diagnosis of peroxisomal disorders.

J Biochem 2019 Jan;165(1):67-73

Biochemical Genetics, Sandor Life Sciences Pvt Ltd, Banjara Hills, Road No: 3, Hyderabad, India.

We have established diagnostic thresholds of very long-chain fatty acids (VLCFA) for the differential diagnosis of peroxisomal disorders using the machine learning tools. The plasma samples of 131 controls and 90 cases were tested for VLCFA using gas chromatography-mass spectrometry following stable isotope dilution. These data were used to construct association rules and for recursive partitioning. Read More

View Article and Full-Text PDF
January 2019