HOME PRODUCTS SERVICES COMPANY CONTACT FAQ

Refsum Disease (Refsum's Disease)

Subscribe to New Research on Refsum Disease

An autosomal recessive familial disorder that usually presents in childhood with POLYNEUROPATHY; SENSORINEURAL HEARING LOSS; ICHTHYOSIS; ATAXIA; RETINITIS PIGMENTOSA; and CARDIOMYOPATHIES. (From Joynt, Clinical Neurology, 1991, Ch37, p58-9; Rev Med Interne 1996;17(5):391-8) This condition can be caused by mutation in the genes encoding peroxisomal phytanoyl-CoA hydroxylase or proteins associated peroxisomal membrane, leading to impaired catabolism of PHYTANIC ACID in PEROXISOMES.

Also Known As:

Refsum's Disease; Refsum Syndrome; Syndrome, Refsum's; Heredopathia Atactica Polyneuritiformis; Phytanic Acid Storage Disease; HMSN 4; Hemeralopia Heredoataxia Polyneuritiformis; Hereditary Motor and Sensory Neuropathy, Type IV; Hereditary Type IV Motor and Sensory Neuropathy; Refsum Disease, Phytanic Acid Oxidase Deficiency; Refsum Disease, Phytanoyl-CoA Hydroxylase Deficiency; Refsum's Syndrome; Refsum-Thiebaut Syndrome; Disease, Refsum; Disease, Refsum's; Heredoataxia Polyneuritiformis, Hemeralopia; Polyneuritiformis, Hemeralopia Heredoataxia; Polyneuritiformis, Heredopathia Atactica; Refsum Disease, Phytanoyl CoA Hydroxylase Deficiency; Refsum Thiebaut Syndrome; Refsum-Thiebaut Syndromes; Refsums Disease; Refsums Syndrome; Syndrome, Refsum-Thiebaut; Syndromes, Refsum-Thiebaut; HMSN Type IV; Neuropathy, Hereditary Motor and Sensory, Type IV

Networked: 231 relevant articles (4 outcomes, 16 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Zellweger Syndrome (Zellweger's Syndrome)
2.	Refsum Disease (Refsum's Disease)
3.	Chondrodysplasia Punctata (Stippled Epiphyses)
4.	Fabry Disease (Fabry's Disease)
5.	Lipidoses

Experts

1.	Wanders, Ronald J A: 8 articles (09/2011 - 02/2003)
2.	Reiser, Georg: 8 articles (08/2011 - 10/2004)
3.	Wanders, R J A: 8 articles (12/2007 - 07/2004)
4.	Wierzbicki, Anthony S: 6 articles (11/2010 - 03/2002)
5.	Schönfeld, Peter: 6 articles (07/2006 - 01/2004)
6.	Wajner, Moacir: 5 articles (06/2013 - 08/2010)
7.	Kahlert, Stefan: 5 articles (11/2009 - 10/2004)
8.	Wanders, R J: 5 articles (01/2009 - 01/2000)
9.	Komen, J C: 5 articles (12/2007 - 07/2004)
10.	Jansen, G A: 5 articles (04/2005 - 01/2000)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Refsum Disease:

1.	Phytanic AcidIBA 01/01/1986 - "However, a few patients with proven Refsum's disease have eliminated their phytanic acid stores by dietary means. " 04/01/1998 - "This study explored the effects of plasma phytanic acid on SLC kinetics in nine Caucasian patients with Refsum's disease and in age- and sex-matched Caucasian control subjects. " 09/01/1995 - "These studies suggest that the alpha-hydroxylation step of phytanic acid oxidation, which has been shown to be defective in Refsum disease, is located in peroxisomes." 01/01/1987 - "The 17 patients with Refsum's disease in the present study had serum phytanic acid values differing from 73 to less than 0.5 mg/dl (normal). " 02/01/1971 - "Studies in patients with the Refsum syndrome show that accumulation of phytanic acid stems from a metabolic error in the pathway for its oxidative degradation. "
2.	PhytolIBA 01/01/1985 - "With regard to sterol composition, data are presented which suggest that an altered sterol is induced in Refsum's disease fibroblasts by the presence of phytol in the growth medium. " 01/01/1985 - "Fibroblasts derived from an individual with Refsum's disease (GM 3896) and a normal control (GM 1717) were grown in the presence of 0, 0.1, 0.2, and 0.3 mM phytol. " 01/01/1985 - "Changes in sterol and phospholipid fatty acid composition in Refsum's disease fibroblasts grown in the presence of phytol." 01/01/1972 - "[Phytol intolerance: Refsum's disease]." 12/15/1965 - "[Studies on the phytol metabolism in lipoidosis heredopathia atactica polyneuritiformis (Refsum's syndrome). "
3.	ChlorophyllIBA 08/01/1980 - "Although the role that chlorophyll-bound phytol plays in Refsum's disease is uncertain, it is advisable that this is eliminated until its role is more clearly identified." 09/01/1968 - "On this basis we conclude that the major portion of the phytanic acid that accumulates in Refsum's disease could not be derived from dietary chlorophyll." 09/01/1968 - "It was concluded that not more than about 5% of the ingested chlorophyll phytol is absorbed by man, whether normal or afflicted with Refsum's disease. " 09/01/1968 - "Absorption of chlorophyll phytol in normal man and in patients with Refsum's disease." 02/01/2005 - "The saturated branched chain fatty acid, phytanic acid, a degradation product of chlorophyll, accumulates in Refsum disease, an inherited peroxisomal disorder with neurological clinical features. "
4.	Protons (Proton)IBA 04/09/1987 - "The ability of phytanic acid to act as a proton carrier may help to explain the toxicity of phytanic acid in Refsum's disease, a metabolic disorder in which phytanic acid accumulates to high levels in plasma, cells and tissues."
5.	Ethyl Ether (Ether)IBA 05/01/1988 - "Patients with RCDP had three characteristic biochemical abnormalities: (1) profound defect in plasmalogen (ether lipid) synthesis, which is significantly greater than the analogous defect in Zellweger syndrome or neonatal ALD; (2) reduction of phytanic acid oxidation activity to 1% to 5% of control, similar to that observed in Refsum disease, Zellweger syndrome, and neonatal ALD; (3) presence of the unprocessed form of peroxisomal 3-oxoacyl-coenzyme A thiolase in the postmortem liver of two patients. "
6.	Acetyl-CoA C-Acyltransferase (beta Ketothiolase)IBA 05/01/1988 - "Patients with RCDP had three characteristic biochemical abnormalities: (1) profound defect in plasmalogen (ether lipid) synthesis, which is significantly greater than the analogous defect in Zellweger syndrome or neonatal ALD; (2) reduction of phytanic acid oxidation activity to 1% to 5% of control, similar to that observed in Refsum disease, Zellweger syndrome, and neonatal ALD; (3) presence of the unprocessed form of peroxisomal 3-oxoacyl-coenzyme A thiolase in the postmortem liver of two patients. "
7.	phytanoyl-coenzyme A (phytanoyl CoA)IBA 12/01/2003 - "Further studies on the substrate spectrum of phytanoyl-CoA hydroxylase: implications for Refsum disease?" 01/01/2013 - "The single peroxisomal enzyme deficiency group comprises seven different disorders, of which D-bifunctional protein and phytanoyl-CoA hydroxylase (adult Refsum disease) deficiencies are the most frequent. " 12/09/2005 - "Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease." 04/01/2005 - "We found that the C-terminal region of DYRK1A interacts with a brain specific protein, phytanoyl-CoA alpha-hydroxylase-associated protein 1 (PAHX-AP1, also named PHYHIP) which was previously shown to interact with phytanoyl-CoA alpha-hydroxylase (PAHX, also named PHYH), a Refsum disease gene product. " 07/01/2004 - "In adult Refsum disease (ARD), peroxisomal alpha-oxidation is defective, which is caused by mutations in the gene coding for phytanoyl-CoA hydroxylase in the majority of ARD patients. "
8.	Fatty Acids (Saturated Fatty Acids)IBA 01/01/2013 - "Additionally, accumulation of certain fatty acids is a hallmark of the rare genetic disorders, Refsum disease and X-ALD. " 02/01/1984 - "Gas-chromatographic procedure, with pyrolytic methylation of serum fatty acids, in the diagnosis of Refsum's syndrome." 10/02/1967 - "Alpha-oxidation as an alternative pathway for the degradation of branched-chain fatty acids in man, and its failure in patients with Refsum's disease." 01/01/1992 - "Elevated levels of very long chain fatty acids (VLCFA) and/or PHYT are the primary diagnostic markers for all peroxisomal disorders and adult Refsum's disease, respectively. " 07/29/1969 - "Alpha-hydroxy fatty acids in hereditary ataxic polyneuritis (Refsum's disease)."
9.	Retinaldehyde (Retinal)IBA 01/01/2003 - "Clinical features & retinal function in patients with adult Refsum syndrome." 12/01/2001 - "These results obtained with cultured retinal cells suggest that the molecular distortion hypothesis, but not the anti-metabolite hypothesis, could explain the pathogenesis of adult Refsum disease. " 01/01/1995 - "Mild retinal changes in a 47-year-old patient with phytanic acid storage disease." 01/01/1995 - "Retinal arteriovenous communication in retinitis pigmentosa with Refsum's disease-like findings." 06/01/2000 - "A number of ichthyosis syndromes may have retinal abnormalities such as the retinitis pigmentosa-like diffuse rod-cone dystrophy in Refsum's syndrome and the maculopathy in Sjögren-Larsson syndrome. "
10.	pipecolic acidIBA 10/01/1995 - "We present here genome wide linkage analysis of an atypical Refsum disease family where L-pipecolic acid level in blood was also increased, suggesting that the patients suffer from a new peroxisomal disorder intermediate between ARD and Infantile Refsum Disease (IRD, a peroxisomal deficiency disease). " 02/01/1988 - "Our data suggest that some patients with the infantile form of Refsum disease may show some clinical benefit from dietary management and this is reflected biochemically by decreases in the plasma levels of phytanic acid and pipecolic acid." 08/01/1986 - "In recent years a number of biochemical abnormalities have been described in patients with the infantile form of Refsum disease, including the accumulation of very long chain fatty acids, trihydroxycoprostanoic acid and pipecolic acid. " 12/01/1984 - "The plasma of patients with the infantile but not the adult form of Refsum's disease contains increased amounts of pipecolic acid and of at least two abnormal bile acids, one of which has been identified as 3 alpha, 7 alpha, 12 alpha trihydroxy-5 beta-cholestan-26-oic acid. " 04/01/1988 - "In this study we carried out a detailed investigation into different peroxisomal functions in classical Refsum's disease by analyses of plasma (very long chain fatty acids, di- and trihydroxycoprostanoic acid and pipecolic acid) and cultured skin fibroblasts from the patients (de novo plasmalogen biosynthesis, very long chain fatty acid oxidation and amount of particle-bound catalase). "

Therapies and Procedures

1.	Plasmapheresis 01/01/2011 - "Two brothers with Refsum's disease who experienced progressive symptoms despite optimal diet and plasmapheresis were commenced on a novel therapy. " 06/01/2005 - "[Refsum's disease with severe neuropathy: efficiency of the diet and plasmapheresis]." 01/01/1991 - "We describe a patient with Refsum's disease in whom long-term plasmapheresis did not improve clinical, biochemical or electrophysiological parameters." 01/01/1985 - "Refsum's disease: management by diet and plasmapheresis." 05/01/1981 - "Renal hemodynamic and tubular functions were measured in a patient with Refsum's disease before and after 12 weeks of twice-weekly plasmaphereses. "
2.	Cochlear Implantation 06/01/2008 - "This study reports our experience with two patients with Refsum's disease who underwent successful cochlear implantation. " 06/01/2014 - "Bilateral cochlear implantation is an important strategy in the improvement of hearing and quality of life in individuals with Refsum's disease." 06/01/2014 - "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. " 06/01/2014 - "Refsum's disease and cochlear implantation." 06/01/2008 - "Cochlear implantation in Refsum's disease."
3.	Plasma Exchange 01/01/1991 - "Long-term plasma exchange in a case of Refsum's disease." 02/01/1989 - "A child with Refsum's disease: successful treatment with diet and plasma exchange." 01/01/1985 - "A case of Refsum's disease treated by serial plasma exchanges together with a moderate low phytanate diet is reported. " 07/01/1991 - "Five cases of heredopathia atactica polyneuritiformis (HAP--Refsum's disease) were treated by serial plasma exchanges. " 07/01/1991 - "Plasma exchange in the treatment of Refsum's disease (heredopathia atactica polyneuritiformis)."
4.	Blood Component Removal (Apheresis) 04/01/2015 - "The indication of apheresis in Refsum's disease and the chylomicronemia syndrome is described. " 01/01/2012 - "We report on the long-term lipid apheresis treatment of four patients with severe Refsum's disease. " 01/01/2012 - "Long-term strategies for the treatment of Refsum's disease using therapeutic apheresis." 01/01/1999 - "Phytanic acid storage disease (Refsum's disease): clinical characteristics, pathophysiology and the role of therapeutic apheresis in its management." 01/01/2012 - "Extracorporeal elimination of lipoprotein-phytanic acid complexes by lipid apheresis represents a pathophysiologically guided therapeutic approach, resulting in long-term improvement or stabilization of overall rehabilitation in patients with progressive Refsum's disease."
5.	Ketogenic Diet 10/01/2007 - "Regimens applicable in adult neurology include low protein diet (phenylketonuria, homocystinuria, urea cycle disorders, organic acidurias), low fatty acid diets (fatty acid B oxidation defects, adrenomyeloneuropathy, Refsum's disease) and ketogenic diet (pyruvate dehydrogenase deficiency, glucose transporter (GLUT1) deficiency, refractory epilepsy). "