ARD
MCID: RFS001
MIFTS: 72

Refsum Disease (ARD) malady

Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Skin diseases categories

Summaries for Refsum Disease

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22Genetics Home Reference, 44NIH Rare Diseases, 45NINDS, 66Wikipedia, 48OMIM, 20GeneReviews, 34MalaCards
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NIH Rare Diseases:44 Refsum disease is an inherited condition that causes vision loss, loss of smell (anosmia), and a variety of other signs and symptoms. the vision loss associated with refsum disease is caused by an eye disorder called retinitis pigmentosa. other features can include bone abnormalities of the hands and feet; progressive muscle weakness and wasting; poor balance and coordination (ataxia); hearing loss; arrhythmiasĀ and heart abnormalities; and dry, scaly skin (ichthyosis). refsum disease can result from mutations in the phyh gene or the pex7 gene and is inherited in an autosomal recessive pattern. last updated: 11/9/2011

MalaCards: Refsum Disease, also known as heredopathia atactica polyneuritiformis, is related to infantile refsum disease and peroxisome biogenesis disorder 2b, and has symptoms including ptosis, peripheral neuropathy and dry/squaly skin/exfoliation. An important gene associated with Refsum Disease is PHYH (phytanoyl-CoA 2-hydroxylase), and among its related pathways is Peroxisome. The drugs acetylcysteine and epoprostenol and the compounds acyl-coa and phytanic acid have been mentioned in the context of this disorder. Affiliated tissues include eye, skin and heart, and related mouse phenotypes are liver/biliary system and homeostasis/metabolism.

Genetics Home Reference:22 Refsum disease is an inherited condition that causes vision loss, absence of the sense of smell (anosmia), and a variety of other signs and symptoms.

NINDS:45 Adult Refsum disease (ARD) is a rare genetic disease that causes weakness or numbness of the hands and feet (peripheral neuropathy).

Wikipedia:66 Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis,... more...

Description from OMIM:48 266510,266500,614879

GeneReviews summary for refsum

Aliases & Classifications for Refsum Disease

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9Disease Ontology, 10diseasecard, 20GeneReviews, 44NIH Rare Diseases, 21GeneTests, 23GTR, 22Genetics Home Reference, 45NINDS, 48OMIM, 11DISEASES, 46Novoseek, 50Orphanet, 63UMLS, 41NCIt, 36MeSH, 28ICD9CM, 59SNOMED-CT, 37MESH via Orphanet, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet
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Classifications:



Characteristics (Orphanet epidemiological data):

50
refsum disease:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000; Age of onset: Childhood


Aliases & Descriptions:

refsum disease 9 10 20 44 22 45 48 11 46 50 63
heredopathia atactica polyneuritiformis 9 44 22 45 50
phytanic acid storage disease 20 23 22 45
phytanic acid oxidase deficiency 20 44 50
refsum syndrome 20 21 22
adult refsum disease 20 22
refsum's disease 9 22
hmsn type iv 9 22
hmsn 4 44 50
hereditary motor and sensory neuropathy type iv 22
hereditary motor and sensory neuropathy type 4 50
herditary sensory and motor neuropathy type 4 44
hereditary motorsensory neuropathy iv 20
respiratory distress syndrome, adult 63
hypertrophic neuropathy of refsum 44
disorder of cornification 11 44
classic refsum disease 22
retinitis pigmentosa 63
hmsn iv 22
hsmn iv 9
doc 11 44
crd 22
ard 22


External Ids:

Disease Ontology9 DOID:10582
NCIt41 C85043
MeSH36 D012035
ICD9CM28 356.3
SNOMED-CT59 25362006
MESH via Orphanet37 D012035
ICD10 via Orphanet27 G60.1
SNOMED-CT via Orphanet60 25362006
UMLS via Orphanet64 C0034960

Related Diseases for Refsum Disease

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Sources:
18GeneCards, 19GeneDecks
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Diseases in the Refsum Disease family:

Pex7-Related Refsum Disease Phyh-Related Refsum Disease

Diseases related to Refsum Disease via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 122)
idRelated DiseaseScoreTop Affiliating Genes
1infantile refsum disease31.0PEX1, PEX6, CAT
2peroxisome biogenesis disorder 2b30.4PEX5
3peroxisome disorders30.2PEX5, PEX2, PEX1, PEX7, CAT, PHYH
4rhizomelic chondrodysplasia punctata30.1CAT, PHYH, PEX7
5neonatal adrenoleukodystrophy30.0PEX5, PEX6, PEX1, CAT
6zellweger syndrome30.0PEX5, PEX26, PEX2, PEX6, PEX1, CAT
7adrenoleukodystrophy29.9CAT, PEX26, PEX1, PEX6, PEX5, PEX2
8zellweger spectrum29.9PEX1, PEX6, PEX26, PEX5
9adult respiratory distress syndrome10.6
10neuropathy10.5
11polyneuropathy10.5
12hereditary neuropathies10.5
13cone-rod dystrophy10.3
14refsum disease with increased pipecolic acidemia10.3
15refsum disease, infantile form10.3
16peroxisome biogenesis disorder 1a10.3
17pneumonia10.3
18retinitis10.2
19cortisone reductase deficiency 110.2
20cortisone reductase deficiency 210.2
21influenza10.2
22malaria10.2
23sepsis10.2
24endotheliitis10.2
25retinitis pigmentosa10.1
26chondrodysplasia10.1
27pex7-related refsum disease10.1
28phyh-related refsum disease10.1
29ataxia10.1
30refsum disease, adult, with increased pipecolicacidemia10.1
31spondylometaphyseal dysplasia with cone-rod dystrophy10.1
32charcot-marie-tooth disease with pyramidal features, autosomal dominant10.1
33respiratory failure10.1
34septic shock10.1
35acute chest syndrome10.1
36alcohol abuse10.1
37plasmodium vivax malaria10.1
38miliary tuberculosis10.1
39acute cor pulmonale10.1
40blastomycosis10.1
41disseminated intravascular coagulation10.1
42tuberculosis10.1
43cor pulmonale10.1
44rhyns syndrome10.0PEX7, PHYH
45neuronitis10.0
46fabry disease10.0
47cerebellar ataxia10.0
48night blindness10.0
49lupus nephritis10.0
50respiratory distress syndrome, infant10.0

Graphical network of the top 20 diseases related to Refsum Disease:



Diseases related to refsum disease

Symptoms for Refsum Disease

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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

266500

Clinical features from OMIM:

266510,266500,614879

Symptoms:

50 (show all 38)
  • ptosis
  • peripheral neuropathy
  • dry/squaly skin/exfoliation
  • metacarpal anomalies/archibald's sign
  • cardiac conduction defect/sinoauricular/heart/auriculoventricular/branch block
  • anomalies of ear and hearing
  • anophthalmos/anophthalmia/microphthalmos/microphthalmia
  • anosmia/cacosmia/hypogeusia/hyposmia/olfactory bulb hypoplasia
  • pupillary anomalies/mydriasis/myosis/tonic pupil
  • foot anomalies
  • pes cavus
  • claw toes/retracted toes
  • cardiomyopathy/hypertrophic/dilated
  • anomalies of eyes and vision
  • hypotonia
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • hemiplegia/diplegia/hemiparesia/limb palsy
  • ataxia/incoordination/trouble of the equilibrium
  • nystagmus
  • abnormal eye movements/oculomotor disorder
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • pyramidal syndrome
  • autosomal recessive inheritance
  • psychic/psychomotor regression/dementia/intellectual decline
  • cataract/lens opacification
  • storage liver disease
  • muscle hypotrophy/atrophy/dystrophy/agenesis/amyotrophy
  • renal failure
  • retinopathy
  • visual loss/blindness/amblyopia
  • sensorineural deafness/hearing loss
  • retinitis pigmentosa/retinal pigmentary changes
  • ichthyosis/ichthyosiform dermatitis
  • metabolic anomalies
  • dysostosis/chondrodysplasia/osteodysplasia/osteochondrosis/skeletal dysplasia
  • splenomegaly
  • epiphyseal anomaly

Drugs & Therapeutics for Refsum Disease

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-RT
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Approved drugs:

Search CenterWatch for Refsum Disease

Drug clinical trials:

Search ClinicalTrials for Refsum Disease

Search NIH Clinical Center for Refsum Disease

Search CenterWatch for Refsum Disease

Inferred drug relations via UMLS63/NDF-RT42:

Genetic Tests for Refsum Disease

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21GeneTests, 23GTR
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Genetic tests related to Refsum Disease:

id Genetic test Affiliating Genes
1 Refsum Disease21
2 Phytanic Acid Storage Disease23

Anatomical Context for Refsum Disease

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34MalaCards
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MalaCards organs/tissues related to Refsum Disease:

34
Eye, Skin, Heart, Bone, Liver, Olfactory bulb, Lung, Brain, Testes, Monocytes, Retina, Cortex, Cerebellum

Animal Models for Refsum Disease or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Refsum Disease:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053708.3PHYH, PEX7, PEX2, PEX5
2MP:00053767.8PHYH, CAT, PEX7, PEX2, PEX5

Publications for Refsum Disease

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53PubMed
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Articles related to Refsum Disease:

(show top 50)    (show all 65)
idTitleAuthorsYear
1
Marked inhibition of Na+, K(+)- ATPase activity and the respiratory chain by phytanic acid in cerebellum from young rats: possible underlying mechanisms of cerebellar ataxia in Refsum disease. (23151916)
2013
2
A child with night blindness: preventing serious symptoms of Refsum disease. (22156782)
2012
3
Medical-dental findings and management of a child with infantile Refsum disease: a case report. (22591434)
2012
4
Phytanic acid disturbs mitochondrial homeostasis in heart of young rats: a possible pathomechanism of cardiomyopathy in Refsum disease. (22527938)
2012
5
Phytanic acid and pristanic acid, branched-chain fatty acids associated with Refsum disease and other inherited peroxisomal disorders, mediate intracellular Ca2+ signaling through activation of free fatty acid receptor GPR40. (21570468)
2011
6
Infantile refsum disease with enamel defects: a case report. (21703082)
2011
7
The effectiveness of long-term dietary therapy in the treatment of adult Refsum disease. (20547622)
2010
8
Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. (20850855)
2010
9
Refsum disease due to the splice-site mutation c.135-2A>G before exon 3 of the PHYH gene, diagnosed eight years after detection of retinitis pigmentosa. (17905308)
2008
10
Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. (19004801)
2008
11
Midlife diagnosis of Refsum disease in siblings with retinitis pigmentosa -- the footprint is the clue: a case report. (18336720)
2008
12
Mechanism of toxicity of the branched-chain fatty acid phytanic acid, a marker of Refsum disease, in astrocytes involves mitochondrial impairment. (16386870)
2006
13
Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid. (16737698)
2006
14
Orthotopic liver transplantation from a living-related donor in an infant with a peroxisome biogenesis defect of the infantile Refsum disease type. (15902563)
2005
15
The Refsum disease marker phytanic acid, a branched chain fatty acid, affects Ca2+ homeostasis and mitochondria, and reduces cell viability in rat hippocampal astrocytes. (15649701)
2005
16
Infantile Refsum disease: serial evaluation with MRI. (15480616)
2005
17
Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease. (16186124)
2005
18
Omega-hydroxylation of phytanic acid in rat liver microsomes: implications for Refsum disease. (15102880)
2004
19
Molecular basis of Refsum disease: sequence variations in phytanoyl- CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). (14974078)
2004
20
Changes underlying arrhythmia in the transgenic heart overexpressing Refsum disease gene-associated protein. (14672712)
2004
21
Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease. (12700346)
2003
22
Identification of PEX7 as the second gene involved in Refsum disease. (14713215)
2003
23
Further studies on the substrate spectrum of phytanoyl-CoA hydroxylase: implications for Refsum disease? (12923223)
2003
24
Postnatal expression and distribution of Refsum disease gene associated protein in the rat retina and visual cortex: effect of binocular visual deprivation. (12034140)
2002
25
Effects of phytanic acid on the vitamin E status, lipid composition and physical properties of retinal cell membranes: implications for adult Refsum disease. (11724659)
2001
26
Refsum disease, peroxisomes and phytanic acid oxidation: a review. (11706932)
2001
27
Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution. (10632109)
2000
28
Identification of a brain specific protein that associates with a Refsum disease gene product, phytanoyl-CoA alpha-hydroxylase. (10686344)
2000
29
Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria. (10471774)
1999
30
Transport of phytanic acid on lipoproteins in Refsum disease. (10070615)
1999
31
Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated protein. (10051602)
1999
32
Phytanoyl-CoA hydroxylase deficiency. Enzymological and molecular basis of classical Refsum disease. (10709665)
1999
33
Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. (9671729)
1998
34
Phytanoyl-CoA hydroxylase is not only deficient in classical Refsum disease but also in rhizomelic chondrodysplasia punctata. (9266377)
1997
35
Identification of PAHX, a Refsum disease gene. (9326939)
1997
36
Infantile Refsum disease: neonatal cholestatic jaundice presentation of a peroxisomal disorder. (7533834)
1995
37
Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family. (8595422)
1995
38
Phytanic acid alpha-oxidase deficiency (Refsum disease) presenting in infancy. (7526031)
1994
39
Resistance to erucic acid as a selectable marker for peroxisomal activity: isolation of revertants of an infantile Refsum disease cell line. (7519689)
1994
40
Refsum disease: a defect in the alpha-oxidation of phytanic acid in peroxisomes. (7504046)
1993
41
Refsum Disease (20301527)
1993
42
Plasma lipoproteins and monocyte-macrophages in a peroxisome-deficient system: study of a patient with infantile refsum disease. (1279267)
1992
43
Autopsy findings in two siblings with infantile Refsum disease. (1373019)
1992
44
Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients. (1282471)
1992
45
MR findings in infantile Refsum disease: case report of two family members. (1722384)
1991
46
Infantile Refsum disease. (1722385)
1991
47
Infantile Refsum disease: an inherited peroxisomal disorder. Comparison with Zellweger syndrome and neonatal adrenoleukodystrophy. (2445576)
1987
48
Biosynthesis and maturation of peroxisomal beta-oxidation enzymes in fibroblasts in relation to the Zellweger syndrome and infantile Refsum disease. (2426710)
1986
49
Location of double bonds in two unsaturated forms of phytanic acid from Refsum disease as determined by mass spectrometry. (6190513)
1983
50
Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease. (6160883)
1980

Variations for Refsum Disease

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar), 8dbSNP
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UniProtKB/Swiss-Prot genetic disease variations for Refsum Disease:

65 (show all 15)
id Symbol AA change Variation ID SNP ID
1PHYHp.Asn269HisVAR_005525
2PHYHp.Arg275TrpVAR_005526rs28939671
3PHYHp.Pro173SerVAR_017483
4PHYHp.Gln176LysVAR_017484rs28939672
5PHYHp.Asp177GlyVAR_017485
6PHYHp.Trp193ArgVAR_017486
7PHYHp.Glu197GlnVAR_017487
8PHYHp.Ile199PheVAR_017488
9PHYHp.Gly204SerVAR_017489rs28939673
10PHYHp.His220TyrVAR_017490
11PHYHp.Arg245GlnVAR_017491rs62619919
12PHYHp.Phe257SerVAR_017492
13PHYHp.Arg275GlnVAR_017493rs28939674
14PHYHp.Asn83TyrVAR_018619
15PHYHp.His175ArgVAR_018631

Clinvar genetic disease variations for Refsum Disease:

1 (show all 14)
id Gene Name Type Significance SNP ID Assembly Location
1RHONM_000539.3(RHO): c.403C> T (p.Arg135Trp)single nucleotide variantPathogenicrs104893775GRCh37Chr 3, 129249760: 129249760
2RHONM_000539.3(RHO): c.44A> G (p.Asn15Ser)single nucleotide variantPathogenicrs104893786GRCh37Chr 3, 129247620: 129247620
3PDE6BNM_000283.3(PDE6B): c.1669C> T (p.His557Tyr)single nucleotide variantPathogenicrs121918581GRCh37Chr 4, 655977: 655977
4RPE65NM_000329.2(RPE65): c.1543C> T (p.Arg515Trp)single nucleotide variantPathogenicrs121917745GRCh37Chr 1, 68895518: 68895518
5RDH12NM_152443.2(RDH12): c.377C> T (p.Ala126Val)single nucleotide variantPathogenicrs202126574GRCh37Chr 14, 68192801: 68192801
6USH2ANM_206933.2(USH2A): c.2276G> T (p.Cys759Phe)single nucleotide variantPathogenicrs80338902GRCh37Chr 1, 216420460: 216420460
7USH2ANM_206933.2(USH2A): c.14020A> G (p.Arg4674Gly)single nucleotide variantPathogenicrs80338904GRCh37Chr 1, 215844427: 215844427
8PEX7NM_000288.3(PEX7): c.-45C> Tsingle nucleotide variantPathogenicrs267608252GRCh37Chr 6, 137143759: 137143759
9USH2ANM_206933.2(USH2A): c.2299delG (p.Glu767Serfs)deletionPathogenicrs80338903GRCh37Chr 1, 216420437: 216420437
10USH2ANM_206933.2(USH2A): c.8559-2A> Gsingle nucleotide variantPathogenicrs397518039GRCh37Chr 1, 216051224: 216051224
11TULP1NM_003322.4(TULP1): c.1145T> C (p.Phe382Ser)single nucleotide variantPathogenicrs121909076GRCh37Chr 6, 35471593: 35471593
12PEX7NM_000288.3(PEX7): c.340-10A> Gsingle nucleotide variantPathogenicrs267608255GRCh37Chr 6, 137166743: 137166743
13PRPH2NM_000322.4(PRPH2): c.736T> C (p.Trp246Arg)single nucleotide variantPathogenicrs61755817GRCh37Chr 6, 42672195: 42672195
14RPE65NM_000329.2(RPE65): c.118G> A (p.Gly40Ser)single nucleotide variantPathogenicrs61751281GRCh37Chr 1, 68912520: 68912520

Expression for genes affiliated with Refsum Disease

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Refsum Disease

Search GEO for disease gene expression data for Refsum Disease.

Pathways for genes affiliated with Refsum Disease

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51PathCards, 31KEGG
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Pathways related to Refsum Disease according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
16.4PHYH, CAT, PEX7, PEX1, PEX6, PEX2

Compounds for genes affiliated with Refsum Disease

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46Novoseek
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Compounds related to Refsum Disease according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1acyl-coa469.3PEX6, PEX5
2phytanic acid469.0PHYH, CAT
3lipid467.7PHYH, CAT, PEX1, PEX2, PEX5

GO Terms for genes affiliated with Refsum Disease

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17Gene Ontology
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Cellular components related to Refsum Disease according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1integral component of peroxisomal membraneGO:0057799.2PEX26, PEX2
2peroxisomal matrixGO:0057828.2PEX5, PEX7, CAT, PHYH
3cytosolGO:0058297.7CAT, PEX7, PEX1, PEX6, PEX5
4peroxisomal membraneGO:0057787.6PEX5, PEX2, PEX6, PEX1, CAT
5peroxisomeGO:0057777.0PHYH, CAT, PEX7, PEX1, PEX6, PEX26

Biological processes related to Refsum Disease according to GeneCards/GeneDecks:

(show all 10)
idNameGO IDScoreTop Affiliating Genes
1ATP catabolic processGO:0062009.5PEX1, PEX6
2protein import into peroxisome membraneGO:0450469.5PEX26, PEX5
3protein import into peroxisome matrix, translocationGO:0165619.4PEX6, PEX5
4very long-chain fatty acid metabolic processGO:0000389.2PEX2, PEX5
5fatty acid beta-oxidationGO:0066359.1PEX5, PEX2, PEX7
6protein targeting to peroxisomeGO:0066259.1PEX1, PEX6, PEX5
7neuron migrationGO:0017649.0PEX5, PEX2, PEX7
8peroxisome organizationGO:0070318.9PEX2, PEX6, PEX1, PEX7
9protein tetramerizationGO:0512628.7CAT, PEX5
10protein import into peroxisome matrixGO:0165588.3PEX7, PEX1, PEX2, PEX26, PEX5

Molecular functions related to Refsum Disease according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1ATPase activity, coupledGO:0426239.5PEX6, PEX1
2protein complex bindingGO:0324039.0PEX1, PEX6, PEX26
3protein C-terminus bindingGO:0080228.5PEX1, PEX6, PEX26, PEX5
4enzyme bindingGO:0198998.4PEX5, PEX7, CAT
5protein bindingGO:0055157.6PHYH, PEX1, PEX6, PEX2, PEX26, PEX5

Products for genes affiliated with Refsum Disease

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  • Antibodies
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Sources for Refsum Disease

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet