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    941 results match your criteria Refsum Disease

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    Clinical and Laboratory Diagnosis of Peroxisomal Disorders.
    Methods Mol Biol 2017 ;1595:329-342
    Department Paediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, AZ, 1105, The Netherlands.
    The peroxisomal disorders (PDs) are a heterogeneous group of genetic diseases in man caused by an impairment in peroxisome biogenesis or one of the metabolic functions of peroxisomes. Thanks to the revolutionary technical developments in gene sequencing methods and their increased use in patient diagnosis, the field of genetic diseases in general and peroxisomal disorders in particular has dramatically changed in the last few years. Indeed, several novel peroxisomal disorders have been identified recently and in addition it has been realized that the phenotypic spectrum of patients affected by a PD keeps widening, which makes clinical recognition of peroxisomal patients increasingly difficult. Read More

    Phytanic acid consumption and human health, risks, benefits and future trends: A review.
    Food Chem 2017 Apr 18;221:237-247. Epub 2016 Oct 18.
    Departamento de Quimica Analitica, Nutricion y Bromatologia, Facultad de Veterinaria, Universidade de Santiago de Compostela, Pabellón 4, Planta Baja, 27002 Lugo, Spain.
    Phytanic acid is a methyl-branched fatty acid present in the human diet, derived from the enzymatic degradation of phytol and subsequently oxidized by the rumenal microbiota and certain marine organisms. Consequently, phytanic acid is carried into the human body by means of food ingestion, mostly via red meat, dairy products and fatty marine foods. This fatty acid accumulates in people with some peroxisomal disorders and is traditionally related to neurological damage. Read More

    Phytanic acid attenuates insulin-like growth factor-1 activity via nitric oxide-mediated γ-secretase activation in rat aortic smooth muscle cells: possible implications for pathogenesis of infantile Refsum disease.
    Pediatr Res 2017 Mar 25;81(3):531-536. Epub 2016 Nov 25.
    Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
    Background: Infantile Refsum disease (IRD), a peroxisomal disease with defective phytanic acid oxidation, causes neurological impairment and development delay. Insulin-like growth factor-1 (IGF-1) regulates child development and to understand molecular mechanism(s) of IRD, we examined the effect of phytanic acid (PA) on IGF-1 activity.

    Methods: Bromodeoxyuridine (BrdU) incorporation was measured in rat aortic smooth muscle cell (SMC) cultures following treatment with fetal bovine serum (FBS), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) or IGF-1 in the absence or presence of PA. Read More

    Lipid profiles in schizophrenia associated with clinical traits: a five year follow-up study.
    BMC Psychiatry 2016 Aug 25;16:299. Epub 2016 Aug 25.
    NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Background: Alterations in serum and membrane lipids may be involved in schizophrenia pathophysiology. It is not known whether lipid profiles are associated with disease severity or current symptom level.

    Methods: Clinical and lipid data were gathered from 55 patients with schizophrenia admitted to psychiatric emergency wards in an acute stage of the disease (T1). Read More

    Keys to overcoming the challenge of diagnosing autosomal recessive spinocerebellar ataxia.
    Neurologia 2016 Jul 23. Epub 2016 Jul 23.
    Servicio de Neurología, Complexo Hospitalario Universitario, Santiago de Compostela, España. Electronic address:
    Introduction: Autosomal recessive spinocerebellar ataxia refers to a large group of diseases affecting the cerebellum and/or its connections, although they may also involve other regions of the nervous system. These diseases are accompanied by a wide range of systemic manifestations (cardiopathies, endocrinopathies, skeletal deformities, and skin abnormalities).

    Development: This study reviews current knowledge of the most common forms of autosomal recessive spinocerebellar ataxia in order to provide tips that may facilitate diagnosis. Read More

    Homocysteine, B Vitamins, and Cognitive Impairment.
    Annu Rev Nutr 2016 Jul;36:211-39
    OPTIMA, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom; email:
    Moderately elevated plasma total homocysteine (tHcy) is a strong modifiable risk factor for vascular dementia and Alzheimer's disease. Prospectively, elevated tHcy is associated with cognitive decline, white matter damage, brain atrophy, neurofibrillary tangles, and dementia. Most homocysteine-lowering trials with folate and vitamins B6 and/or B12 tested as protective agents against cognitive decline were poorly designed by including subjects unlikely to benefit during the trial period. Read More

    Phytanic acid activates NADPH oxidase through transactivation of epidermal growth factor receptor in vascular smooth muscle cells.
    Lipids Health Dis 2016 Jun 10;15:105. Epub 2016 Jun 10.
    Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
    Background: Phytanic acid (PA) has been implicated in development of cancer and its defective metabolism is known to cause life-threatening conditions, such as Refsum disease, in children. To explore molecular mechanisms of phytanic acid-induced cellular pathology, we investigated its effect on NADPH oxidase (NOX) and epidermal growth factor receptor (EGFR) in rat aortic smooth muscle cells (RASMC).

    Methods: Smooth muscle cells were isolated from rat aortae using enzymic digestion with collagenase and elastase. Read More

    Living-Donor Liver Transplantation From a Heterozygous Parent for Infantile Refsum Disease.
    Pediatrics 2016 Jun;137(6)
    Organ Transplantation Center, and.
    Infantile Refsum disease (IRD) is a rare autosomal recessive disorder of peroxisome biogenesis characterized by generalized peroxisomal metabolic dysfunction, including accumulation of very long-chain fatty acids (VLCFAs) and phytanic acid (PA), as well as decreased plasmalogen contents (PL). An effective therapy for this intractable disease has not been established, and only supportive management with docosahexaenoic acid supplementation and low PA diet has been reported so far. A boy of 3 years and 8 months presented with facial dysmorphism, transaminitis, and psychomotor retardation. Read More

    Brain Lipotoxicity of Phytanic Acid and Very Long-chain Fatty Acids. Harmful Cellular/Mitochondrial Activities in Refsum Disease and X-Linked Adrenoleukodystrophy.
    Aging Dis 2016 Mar 15;7(2):136-49. Epub 2016 Mar 15.
    Institut für Neurobiochemie (Institut für Inflammation und Neurodegeneration), Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
    It is increasingly understood that in the aging brain, especially in the case of patients suffering from neurodegenerative diseases, some fatty acids at pathologically high concentrations exert detrimental activities. To study such activities, we here analyze genetic diseases, which are due to compromised metabolism of specific fatty acids, either the branched-chain phytanic acid or very long-chain fatty acids (VLCFAs). Micromolar concentrations of phytanic acid or of VLCFAs disturb the integrity of neural cells by impairing Ca(2+) homeostasis, enhancing oxidative stress or de-energizing mitochondria. Read More

    Zellweger syndrome with severe malnutrition, immunocompromised state and opportunistic infections.
    BMJ Case Rep 2016 Apr 18;2016:10.1136/bcr-2015-214283. Epub 2016 Apr 18.
    Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
    Peroxisome biogenesis disorders are related to a spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterised by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. Increased levels of very long chain fatty acids are the biochemical hallmark and the most common mutations found in the PEX1 gene. Read More

    Clinical and Biochemical Pitfalls in the Diagnosis of Peroxisomal Disorders.
    Neuropediatrics 2016 Aug 18;47(4):205-20. Epub 2016 Apr 18.
    Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
    Peroxisomal disorders are a heterogeneous group of genetic metabolic disorders, caused by a defect in peroxisome biogenesis or a deficiency of a single peroxisomal enzyme. The peroxisomal disorders include the Zellweger spectrum disorders, the rhizomelic chondrodysplasia punctata spectrum disorders, X-linked adrenoleukodystrophy, and multiple single enzyme deficiencies. There are several core phenotypes caused by peroxisomal dysfunction that clinicians can recognize. Read More

    Inherited ichthyosis: Syndromic forms.
    J Dermatol 2016 Mar;43(3):252-63
    Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
    Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, Dorfman-Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. Read More

    Ocular manifestations of genetic skin disorders.
    Clin Dermatol 2016 Mar-Apr;34(2):242-75. Epub 2015 Dec 2.
    The Vision Center, Children's Hospital Los Angeles; Department of Ophthalmology, Keck School of Medicine, University of Southern California, 4650 Sunset Blvd, MS #88, Los Angeles, CA, 90027.
    Genetic skin diseases, or genodermatoses, often have extracutaneous manifestations. Ocular manifestations in particular can have significant clinical implications, like blindness. Other manifestations, such as the corneal opacities that occur in X-linked ichthyosis, are asymptomatic but characteristic of a particular genodermatosis. Read More

    Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease.
    Int J Clin Pract 2016 Mar 22;70(3):229-35. Epub 2016 Jan 22.
    Adult Refsum Disease Clinic, Chelsea & Westminster Hospital, London, UK.
    Background: Adult Refsum's Disease (ARD) is caused by defects in the pathway for alpha-oxidation of phytanic acid (PA). Treatment involves restricting the dietary intake of phytanic acid by reducing the intake of dairy-derived fat. The adequacy of micronutrient intake in patients with ARD is unknown. Read More

    Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.
    J Alzheimers Dis 2016 ;50(2):547-57
    Division of Geriatric Medicine, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
    A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Read More

    Conventional and advanced MR imaging in infantile Refsum disease.
    Turk J Pediatr 2015 May-Jun;57(3):294-9
    Divisions of Pediatric Nutrition and Metabolism, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
    We report magnetic resonance (MR) imaging findings including diffusion-weighted imaging and proton MR spectroscopy findings in a patient with infantile Refsum disease. The initial diagnosis was made on the basis of history, clinical findings and biochemical studies. Bilateral and symmetrical involvement of the peritrigonal white matter, centrum semiovale, thalami, corpus callosum and corticospinal tracts as assessed by increased T2 signal was highly suggestive of a peroxisomal disorder. Read More

    Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels.
    JIMD Rep 2016 25;26:53-60. Epub 2015 Aug 25.
    Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar/Universidade do Porto, Porto, Portugal.
    Infantile Refsum disease (IRD) is one of the less severe of Zellweger spectrum disorders (ZSDs), a group of peroxisomal biogenesis disorders resulting from a generalized peroxisomal function impairment. Increased plasma levels of very long chain fatty acids (VLCFA) and phytanic acid are biomarkers used in IRD diagnosis. Furthermore, an increased plasma level of phytanic acid is known to be associated with neurologic damage. Read More

    Phytol is lethal for Amacr-deficient mice.
    Biochim Biophys Acta 2015 Oct 4;1851(10):1394-405. Epub 2015 Aug 4.
    Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, FI-90014, Finland; Biocenter Oulu, University of Oulu, Finland. Electronic address:
    α-Methylacyl-CoA racemase (Amacr) catalyzes the racemization of the 25-methyl group in C27-intermediates in bile acid synthesis and in methyl-branched fatty acids such as pristanic acid, a metabolite derived from phytol. Consequently, patients with Amacr deficiency accumulate C27-bile acid intermediates, pristanic and phytanic acid and display sensorimotor neuropathy, seizures and relapsing encephalopathy. In contrast to humans, Amacr-deficient mice are clinically symptomless on a standard laboratory diet, but failed to thrive when fed phytol-enriched chow. Read More

    Reactive nitrogen species mediate oxidative stress and astrogliosis provoked by in vivo administration of phytanic acid in cerebellum of adolescent rats: A potential contributing pathomechanism of cerebellar injury in peroxisomal disorders.
    Neuroscience 2015 Sep 15;304:122-32. Epub 2015 Jul 15.
    Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. Electronic address:
    Phytanic acid (Phyt) accumulates in various peroxisomal diseases including Refsum disease (RD) and Zellweger syndrome (ZS). Since the pathogenesis of the neurological symptoms and especially the cerebellar abnormalities in these disorders are poorly known, we investigated the effects of in vivo intracerebral administration of Phyt on a large spectrum of redox homeostasis parameters in the cerebellum of young rats. Malondialdehyde (MDA) levels, sulfhydryl oxidation, carbonyl content, nitrite and nitrate concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, total (tGS) and reduced glutathione (GSH) levels and the activities of important antioxidant enzymes were determined at different periods after Phyt administration. Read More

    Audiological findings in Infantile Refsum disease.
    Int J Pediatr Otorhinolaryngol 2015 Aug 30;79(8):1366-9. Epub 2015 May 30.
    Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Electronic address:
    Audiological manifestations in a four-year-old child with Infantile Refsum disease are reported. He was born to non-consanguineous parents and had normal birth history and mildly delayed milestones prior to presentation. Clinical features were characterized by neuroregression, retinitis pigmentosa, hearing loss, peripheral neuropathy and white matter signal changes on magnetic resonance imaging. Read More

    Neurological associations in auditory neuropathy spectrum disorder: Results from a tertiary hospital in South India.
    Ann Indian Acad Neurol 2015 Apr-Jun;18(2):171-80
    Department of Ear, Nose and Throat, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
    Aims: To find out the prevalence and types of neurological abnormalities associated in auditory neuropathy spectrum disorder in a large tertiary referral center.

    Settings And Design: A prospective clinical study was conducted on all patients diagnosed with auditory neuropathy spectrum disorder in the ear, nose, and throat (ENT) and neurology departments during a 17-month period. Patients with neurological abnormalities on history and examination were further assessed by a neurologist to determine the type of disorder present. Read More

    Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
    Am J Clin Nutr 2015 Jul 15;102(1):215-21. Epub 2015 Apr 15.
    From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom;
    Background: Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia.

    Objective: We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). Read More

    Phytanic acid induces Neuro2a cell death via histone deacetylase activation and mitochondrial dysfunction.
    Neurotoxicol Teratol 2015 Mar-Apr;48:33-9. Epub 2015 Jan 22.
    Department of Epigenetic Medicine, University of Yamanashi, Yamanashi 409-3898, Japan. Electronic address:
    Phytanic acid is a branched fatty acid that is a metabolic intermediate of chlorophyll. In this study, the effects of phytanic acid on Histone deacetylase (Hdac) activity were examined in an in vitro enzyme assay and in neuronal Neuro2a cells. Several fatty acids have been shown to be Hdac inhibitors, but phytanic acid enhanced the enzyme activity in vitro. Read More

    Cerebellar transcriptional alterations with Purkinje cell dysfunction and loss in mice lacking PGC-1α.
    Front Cell Neurosci 2014 6;8:441. Epub 2015 Jan 6.
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA.
    Alterations in the expression and activity of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (ppargc1a or PGC-1α) have been reported in multiple movement disorders, yet it is unclear how a lack of PGC-1α impacts transcription and function of the cerebellum, a region with high PGC-1α expression. We show here that mice lacking PGC-1α exhibit ataxia in addition to the previously described deficits in motor coordination. Using q-RT-PCR in cerebellar homogenates from PGC-1α(-/-) mice, we measured expression of 37 microarray-identified transcripts upregulated by PGC-1α in SH-SY5Y neuroblastoma cells with neuroanatomical overlap with PGC-1α or parvalbumin (PV), a calcium buffer highly expressed by Purkinje cells. Read More

    Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop.
    Thromb Haemost 2015 Mar 22;113(3):452-63. Epub 2015 Jan 22.
    Eveline Baumgart-Vogt, Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, 35392 Giessen, Germany, E-mail:
    It is well established that the heart is strongly dependent on fatty acid metabolism. In cardiomyocytes there are two distinct sites for the β-oxidisation of fatty acids: the mitochondrion and the peroxisome. Although the metabolism of these two organelles is believed to be tightly coupled, the nature of this relationship has not been fully investigated. Read More

    Refsum Disease Presenting with a Late-Onset Leukodystrophy.
    JIMD Rep 2015 21;19:7-10. Epub 2015 Jan 21.
    Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France,
    Adult Refsum disease is an autosomal recessive peroxisomal disorder characterized by phytanic acid storage. Clinical symptoms usually begin in late childhood before the age of 20. Typical clinical presentation includes nyctalopia caused by retinitis pigmentosa, and anosmia. Read More

    Infantile Refsum disease in a young adult: case presentation and brief review.
    Retin Cases Brief Rep 2014 ;8(1):56-9
    Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
    Purpose: To review and describe findings, pathophysiology, and management of infantile Refsum disease in a young adult, and to compare with those of classic Refsum Disease.

    Methods: Retrospective chart and digital photography review.

    Results: A 25-year-old woman with a diagnosis of infantile Refsum disease presented with progressively decreasing vision. Read More

    Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar bodies and stratum corneum barrier lipid organization.
    Arch Dermatol Res 2014 Oct 12;306(8):731-7. Epub 2014 Jun 12.
    Global Research and Development, Ashland, Inc., Bridgewater, NJ, USA.
    Classic Refsum disease (RD) is a rare, autosomal recessively-inherited disorder of peroxisome metabolism due to a defect in the initial step in the alpha oxidation of phytanic acid (PA), a C16 saturated fatty acid with four methyl side groups, which accumulates in plasma and lipid enriched tissues (please see van den Brink and Wanders, Cell Mol Life Sci 63:1752-1765, 2006). It has been proposed that the disease complex in RD is in part due to the high affinity of phytanic acid for retinoid X receptors and peroxisome proliferator-activated receptors. Structurally, epidermal hyperplasia, increased numbers of cornified cell layers, presence of cells with lipid droplets in stratum basale and reduction of granular layer to a single layer have been reported by Blanchet-Bardon et al. Read More

    Refsum's disease and cochlear implantation.
    Ann Otol Rhinol Laryngol 2014 Jun;123(6):425-7
    Objectives: The objective was to describe a case of bilateral cochlear implantation in a 59-year-old man with hearing and visual impairment due to Refsum's disease.

    Method: A retrospective case review was performed.

    Results: After cochlear implantation, the patient demonstrated much improved audiometric performance and reported improved sound localization. Read More

    Cobalamin and folate status in 6 to 35 months old children presenting with acute diarrhea in Bhaktapur, Nepal.
    PLoS One 2014 3;9(3):e90079. Epub 2014 Mar 3.
    Centre for International Health, University of Bergen, Norway; Medical Microbiology, Innlandet Hospital Trust, Lillehammer, Norway.
    Background: Cobalamin and folate are essential micronutrients and are important in DNA and RNA synthesis, cell proliferation, growth, hematopoiesis, and cognitive function. However, data on cobalamin and folate status are lacking particularly from young children residing in low and middle income countries.

    Objective: To measure cobalamin and folate status and identifies their predictors among 6 to 35 months old children presenting with acute diarrhea. Read More

    Pipecolic acid induces oxidative stress in vitro in cerebral cortex of young rats and the protective role of lipoic acid.
    Metab Brain Dis 2014 Mar 12;29(1):175-83. Epub 2013 Dec 12.
    Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
    Pipecolic acid (PA) levels are increased in severe metabolic disorders of the central nervous system such as Zellweger syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and hyperlysinemia. The affected individuals present progressive neurological dysfunction, hypotonia and growth retardation. The mechanisms of brain damage of these disorders remain poorly understood. Read More

    Carrier rates of four single-gene disorders in Croatian Bayash Roma.
    Genet Test Mol Biomarkers 2014 Feb 4;18(2):83-7. Epub 2013 Nov 4.
    Institute for Anthropological Research , Zagreb, Croatia .
    To assess how specific population history, different migration routes, isolation, and endogamy practices contributed to the distribution of several rare diseases found in specific Roma groups, we conducted a population-based research study of rare disease mutations in Croatian Vlax Roma. We tested a total of 427 subjects from Baranja and Međimurje for the presence of four mutations causing hereditary motor and sensory neuropathy type Lom (HMSNL), GM1 gangliosidosis (GM1), congenital cataracts, facial dysmorphism and neuropathy (CCFDN), and limb girdle muscle dystrophy type 2C (LGMD2C), using the RFLP-PCR method to estimate carrier frequencies. We identified a total of four individuals heterozygous for the mutation causing HMSNL in the Baranja population, with a carrier rate amounting to 1. Read More

    Exonic duplication CNV of NDRG1 associated with autosomal-recessive HMSN-Lom/CMT4D.
    Genet Med 2014 May 17;16(5):386-94. Epub 2013 Oct 17.
    1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA [3] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA [4] Texas Children's Hospital, Houston, Texas, USA.
    Purpose: Copy-number variations as a mutational mechanism contribute significantly to human disease. Approximately one-half of the patients with Charcot-Marie-Tooth (CMT) disease have a 1.4 Mb duplication copy-number variation as the cause of their neuropathy. Read More

    Formation and functions of the corneocyte lipid envelope (CLE).
    Biochim Biophys Acta 2014 Mar 27;1841(3):314-8. Epub 2013 Sep 27.
    Dermatology Services, Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Dermatology, University of California, San Francisco, CA, USA.
    Corneocytes in mammalian stratum corneum are surrounded by a monolayer of covalently bound ω-OH-ceramides that form the corneocyte (-bound) lipid envelope (CLE). We review here the structure, composition, and possible functions of this structure, with insights provided by inherited and acquired disorders of lipid metabolism. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Read More

    [Chronic ataxia in childhood].
    Medicina (B Aires) 2013 ;73 Suppl 1:38-48
    Neurología pediátrica, Universidad de Chile, Chile. E-mail:
    Chronic ataxias are an heterogeneous group of disorders that affect the child at different ages. Thus, the congenital forms, generally non progressive are observed from first months of life and are expressed by hypotonia and motor delay long before the ataxia became evident. The cerebral magnetic resonance images (MRI) may be diagnostic in some pictures like Joubert syndrome. Read More

    CMT4D (NDRG1 mutation): genotype-phenotype correlations.
    J Peripher Nerv Syst 2013 Sep;18(3):261-5
    Service et Laboratoire de Neurologie, Centre de Référence Neuropathies Périphériques Rares, CHU Limoges, Limoges, France.
    Charcot-Marie-Tooth (CMT) disease is a heterogeneous condition with a large number of clinical, electrophysiological and pathological phenotypes. More than 40 genes are involved. We report a child of gypsy origin with an autosomal recessive demyelinating phenotype. Read More

    Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia.
    J Appl Genet 2013 Nov 31;54(4):455-60. Epub 2013 Aug 31.
    Department of Biology, Faculty of Humanities and Natural Sciences, University of Presov, Ul. 17. Novembra 1, 08116, Presov, Slovakia,
    Autosomal recessive forms of Charcot-Marie-Tooth disease (CMT) account for less than 10 % of all CMT cases, but are more frequent in the populations with a high rate of consanguinity. Roma (Gypsies) are a transnational minority with an estimated population of 10 to 14 million, in which a high degree of consanguineous marriages is a generally known fact. Similar to the other genetically isolated founder populations, the Roma harbour a number of unique or rare autosomal recessive disorders, caused by "private" founder mutations. Read More

    NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation.
    J Cell Sci 2013 Sep 26;126(Pt 17):3961-71. Epub 2013 Jun 26.
    Institute of Biomedicine, Anatomy, University of Helsinki, Helsinki, Finland.
    N-myc downstream-regulated gene 1 (NDRG1) mutations cause Charcot-Marie-Tooth disease type 4D (CMT4D). However, the cellular function of NDRG1 and how it causes CMT4D are poorly understood. We report that NDRG1 silencing in epithelial cells results in decreased uptake of low-density lipoprotein (LDL) due to reduced LDL receptor (LDLR) abundance at the plasma membrane. Read More

    Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives.
    Dev Disabil Res Rev 2013 ;17(3):187-96
    Department of Human Genetics, McGill University, Quebec, Canada.
    The peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders in which peroxisome assembly is impaired, leading to multiple peroxisome enzyme deficiencies, complex developmental sequelae and progressive disabilities. Mammalian peroxisome assembly involves the protein products of 16 PEX genes; defects in 14 of these have been shown to cause PBD. Three broad phenotypic groups are described on a spectrum of severity: Zellweger syndrome is the most severe, neonatal adrenoleukodystrophy is intermediate and infantile Refsum disease is less severe. Read More

    Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment.
    Proc Natl Acad Sci U S A 2013 Jun 20;110(23):9523-8. Epub 2013 May 20.
    Functional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
    Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer's disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0. Read More

    CYP4 enzymes as potential drug targets: focus on enzyme multiplicity, inducers and inhibitors, and therapeutic modulation of 20-hydroxyeicosatetraenoic acid (20-HETE) synthase and fatty acid ω-hydroxylase activities.
    Curr Top Med Chem 2013 ;13(12):1429-40
    Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 98195, USA.
    The Cytochrome P450 4 (CYP4) family of enzymes in humans is comprised of thirteen isozymes that typically catalyze the ω-oxidation of endogenous fatty acids and eicosanoids. Several CYP4 enzymes can biosynthesize 20- hydroxyeicosatetraenoic acid, or 20-HETE, an important signaling eicosanoid involved in regulation of vascular tone and kidney reabsorption. Additionally, accumulation of certain fatty acids is a hallmark of the rare genetic disorders, Refsum disease and X-ALD. Read More

    Child neurology: Zellweger syndrome.
    Neurology 2013 May;80(20):e207-10
    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
    Zellweger syndrome (ZS) is a severe manifestation of disease within the spectrum of peroxisome biogenesis disorders that includes neonatal adrenoleukodystrophy, infantile Refsum disease, and rhizomelic chondroplasia punctata. Patients with ZS present in the neonatal period with a characteristic phenotype of distinctive facial stigmata, pronounced hypotonia, poor feeding, hepatic dysfunction, and often seizures and boney abnormalities. In patients with ZS, a mutation in one of the PEX genes coding for a peroxin (a peroxisome assembly protein) creates functionally incompetent organelles causing an accumulation of very long chain fatty acids (VLCFA), among other complications. Read More

    Peroxisomal disorders.
    Handb Clin Neurol 2013 ;113:1593-609
    Department of Pediatric Neurology, INSERM UM745, University Paris-Descartes, Hôpital Bicêtre-Paris Sud, Paris, France. Electronic address:
    The peroxisomal disorders represent a group of genetic diseases in man in which there is an impairment in one or more peroxisomal functions. The peroxisomal disorders are subdivided into three subgroups comprising: (1) the peroxisome biogenesis disorders (PBDs); (2) the single peroxisomal (enzyme-) protein deficiencies; and (3) the single peroxisomal substrate transport deficiencies. The PBD group comprises four different disorders that include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). Read More

    Metabolic neuropathies and myopathies.
    Handb Clin Neurol 2013 ;113:1437-55
    Molecular Medicine and Unit of Neuromuscular and Neurodegenerative Diseases, IRCCS-Children's Hospital Bambino Gesù, Rome, Italy.
    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. Read More

    [Inborn errors of metabolism in adult neurology].
    Rev Neurol (Paris) 2013 Feb;169 Suppl 1:S63-9
    Département de Neurologie, centre de référence maladies lysosomales, Unité fonctionnelle neurométabolique bio-clinique et génétique, Hôpital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, 47 Boulevard de l'Hôpital, 75651 Paris cedex 13, France.
    Inborn errors of metabolism (IEM) are caused by mutations in genes coding for enzymes and other proteins involved in cell metabolism. Many IEM can be treated effectively. Although IEM have usually been considered pediatric diseases, they can present at any age, mostly with neurological and psychiatric symptoms, and therefore constitute an integral subspeciality of neurology. Read More

    Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals.
    Lancet 2013 Mar;381(9871):1029-36
    Norwegian Institute of Public Health and Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
    Background: Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification.

    Methods: In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. Read More

    Newly identified milder phenotype of peroxisome biogenesis disorder caused by mutated PEX3 gene.
    Brain Dev 2013 Oct 14;35(9):842-8. Epub 2012 Dec 14.
    Tokyo Children's Rehabilitation Hospital, Musashimurayama, Tokyo, Japan.
    We identified the first patient with infantile Refsum disease (IRD), a milder phenotype of peroxisome biogenesis disorder (PBD) caused by a mutated PEX3, and investigated the clinical, molecular and cellular characterization in this patient. The patient presented psychomotor regression, late-onset leukodystrophy, peripheral neuropathy, hearing impairment, a renal cyst, and renal hypertension and survived until the age of 36. Furthermore, fibroblasts from the patient indicated a mosaic pattern of catalase-positive particles (peroxisomes) and numerous peroxisomal membrane structures. Read More

    Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E ε4: the Hordaland Homocysteine Study.
    Psychosom Med 2013 Jan 4;75(1):20-9. Epub 2012 Dec 4.
    OPTIMA, Department of Pharmacology, University of Oxford, Oxford, UK.
    Objective: To investigate the cross-sectional relation between metabolic markers of vitamin B(12) status and cognitive performance, and possible effect modification by the presence of depression and apolipoprotein E (ApoE) ε4.

    Methods: This is a population-based study of 1935 participants, aged 71 to 74 years, from Norway. Participants were administered a cognitive test battery, and vitamin B(12) status was assessed by measurements of plasma vitamin B(12), holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine. Read More

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