MCID: RFS006
MIFTS: 62

Refsum Disease, Classic

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Skin diseases, Metabolic diseases

Aliases & Classifications for Refsum Disease, Classic

MalaCards integrated aliases for Refsum Disease, Classic:

Name: Refsum Disease, Classic 57
Refsum Disease 57 12 76 24 53 25 54 59 75 37 13 55 44 15 40 73
Heredopathia Atactica Polyneuritiformis 57 12 53 25 54 59 75
Phytanic Acid Oxidase Deficiency 57 76 53 75
Phytanic Acid Storage Disease 25 54 29 6
Refsum Disease, Adult, 1 57 29 6
Adult Refsum Disease 24 25 59
Refsum's Disease 12 25 75
Hmsn Iv 57 25 75
Hereditary Motor and Sensory Neuropathy Iv 57 75
Classic Refsum Disease 25 59
Refsum Syndrome 24 25
Hmsn Type Iv 12 25
Hmsn 4 53 59
Hmsn4 57 75
Hereditary Motor and Sensory Neuropathy Iv; Hmsn4 57
Hereditary Motor and Sensory Neuropathy Type Iv 25
Hereditary Sensory and Motor Neuropathy Type 4 53
Hereditary Motor and Sensory Neuropathy Type 4 59
Phytanic-Coa Hydroxylase Deficiency 59
Hypertrophic Neuropathy of Refsum 53
Disorder of Cornification 11 53
Hsmn Iv 12
Doc 11 53
Crd 25
Ard 25
Rd 75

Characteristics:

Orphanet epidemiological data:

59
refsum disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
affected infants appear normal
symptoms show insidious onset in the late first through third decades


HPO:

32
refsum disease, classic:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Refsum Disease, Classic

OMIM : 57 Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells. However, not all patients show all these features. All patients have accumulation of an unusual branched-chain fatty acid, phytanic acid, in blood and tissues. Other variable features include cardiac dysfunction, nerve deafness, ichthyosis, and multiple epiphyseal dysplasia (review by Skjeldal et al., 1987). Increased levels of phytanic acid can also be found in peroxisomal biogenesis disorders; see Zellweger syndrome (see 214100) (Skjeldal et al., 1987). Infantile Refsum disease (see PBD1B, 601539) is a distinct disorder with a different phenotype and genetic basis. A phenotype clinically indistinguishable from that of classic Refsum disease (PBD9B; 614879), but with a different biochemical profile, can be caused by mutation in the gene encoding peroxin-7 (PEX7; 601757) on chromosome 6q. (266500)

MalaCards based summary : Refsum Disease, Classic, also known as refsum disease, is related to zellweger syndrome and peroxisome biogenesis disorder 1b. An important gene associated with Refsum Disease, Classic is PHYH (Phytanoyl-CoA 2-Hydroxylase), and among its related pathways/superpathways are Peroxisome and Synthesis of bile acids and bile salts. The drugs Betaine and Bile Acids and Salts have been mentioned in the context of this disorder. Affiliated tissues include skin, bone and eye, and related phenotypes are abnormality of epiphysis morphology and ptosis

UniProtKB/Swiss-Prot : 75 Refsum disease: A rare autosomal recessive peroxisomal disorder characterized by the accumulation of the branched-chain fatty acid, phytanic acid, in blood and tissues. Cardinal clinical features are retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF). Half of all patients exhibit generalized, mild to moderate ichthyosis resembling ichthyosis vulgaris. Less constant features are nerve deafness, anosmia, skeletal abnormalities, cataracts and cardiac impairment.

NIH Rare Diseases : 53 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; arrhythmias 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.

NINDS : 54 Adult Refsum disease (ARD) is a rare genetic disease that causes weakness or numbness of the hands and feet (peripheral neuropathy).  Due to a genetic abnormality, people with ARD disease lack the enzyme in peroxisomes that break down phytanic acid, a type of fat found in certain foods.  As a result, toxic levels of phytanic acid build up in the brain, blood, and other tissues.  The disease usually begins in late childhood or early adulthood with increasing night blindness due to degeneration of the retina (retinitis pigmentosa).  If the disease progresses, other symptoms may include deafness, loss of the sense of smell (anosmia), problems with balance and coordination (ataxia), dry and scaly skin (ichthyosis), and heartbeat abnormalities (cardiac arrhythmias).  Some individuals will have shortened bones in their fingers or toes, or a visibly shortened fourth toe.  Although the disease usually appears in early childhood, some people will not develop symptoms until their 40s or 50s.

Genetics Home Reference : 25 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.

Wikipedia : 76 Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis,... more...

GeneReviews: NBK1353

Related Diseases for Refsum Disease, Classic

Diseases related to Refsum Disease, Classic via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 111)
# Related Disease Score Top Affiliating Genes
1 zellweger syndrome 30.3 GNPAT PEX14 PEX16 PEX5
2 peroxisome biogenesis disorder 1b 30.1 CAT GNPAT HSD17B4 PEX14 PEX16 PEX5
3 neonatal adrenoleukodystrophy 30.0 CAT PEX14 PEX16 PEX5 PEX7 SCP2
4 peroxisomal disease 28.3 CAT GNPAT HSD17B4 PEX5 PEX7 PHYH
5 refsum disease, infantile form 12.4
6 refsum disease with increased pipecolic acidemia 12.0
7 respiratory distress syndrome in premature infants 11.8
8 peroxisome biogenesis disorder 9b 11.8
9 restrictive dermopathy, lethal 11.6
10 reticular dysgenesis 11.6
11 zellweger spectrum disorder 11.2
12 hereditary motor and sensory neuropathy v 11.1
13 leukodystrophy 11.1
14 peroxisome biogenesis disorder-zellweger syndrome spectrum 11.1
15 respiratory distress syndrome, infant 11.0
16 peroxisome biogenesis disorder 1a 11.0
17 peroxisome biogenesis disorder 2b 10.9
18 peroxisome biogenesis disorder 3b 10.9
19 peroxisome biogenesis disorder 4b 10.9
20 peroxisome biogenesis disorder 5b 10.9
21 peroxisome biogenesis disorder 6b 10.9
22 peroxisome biogenesis disorder 7b 10.9
23 peroxisome biogenesis disorder 11b 10.9
24 renal hypodysplasia/aplasia 1 10.9
25 renal hypodysplasia/aplasia 2 10.9
26 bronchopulmonary dysplasia 10.9
27 radin blood group antigen 10.9
28 adult respiratory distress syndrome 10.9
29 flynn-aird syndrome 10.8
30 peroxisome biogenesis disorder 2a 10.8
31 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 10.8
32 peroxisome biogenesis disorder 3a 10.8
33 peroxisome biogenesis disorder 4a 10.8
34 peroxisome biogenesis disorder 5a 10.8
35 peroxisome biogenesis disorder 6a 10.8
36 peroxisome biogenesis disorder 7a 10.8
37 peroxisome biogenesis disorder 8a 10.8
38 peroxisome biogenesis disorder 8b 10.8
39 peroxisome biogenesis disorder 10a 10.8
40 peroxisome biogenesis disorder 11a 10.8
41 peroxisome biogenesis disorder 12a 10.8
42 peroxisome biogenesis disorder 13a 10.8
43 rud syndrome 10.8
44 retinitis 10.5
45 polyneuropathy 10.4
46 neuropathy 10.4
47 hereditary neuropathies 10.4
48 retinitis pigmentosa 10.3
49 leber congenital amaurosis 4 10.3
50 rhabdomyosarcoma 10.3

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



Diseases related to Refsum Disease, Classic

Symptoms & Phenotypes for Refsum Disease, Classic

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin:
ichthyosis

Skeletal Feet:
pes cavus
shortening of the metatarsals

Head And Neck Nose:
anosmia

Head And Neck Eyes:
sensorineural deafness, progressive

Neurologic Central Nervous System:
increased csf protein with normal cell count

Cardiovascular Heart:
cardiomegaly
cardiomyopathy
cardiac failure (sudden death has been reported)
electrocardiographic abnormalities

Neurologic Peripheral Nervous System:
hyporeflexia
sensory impairment
limb weakness
peripheral sensorimotor neuropathy
limb atrophy
more
Skeletal:
multiple epiphyseal dysplasia

Skeletal Hands:
shortening of the metacarpals

Laboratory Abnormalities:
increased phytanic acid in body tissues and fluids
decreased phytanic acid oxidase activity


Clinical features from OMIM:

266500

Human phenotypes related to Refsum Disease, Classic:

59 32 (show top 50) (show all 52)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of epiphysis morphology 59 32 frequent (33%) Frequent (79-30%) HP:0005930
2 ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000508
3 nystagmus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000639
4 ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001251
5 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
6 respiratory insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0002093
7 developmental regression 59 32 frequent (33%) Frequent (79-30%) HP:0002376
8 abnormal pyramidal signs 59 32 hallmark (90%) Very frequent (99-80%) HP:0007256
9 cataract 59 32 hallmark (90%) Very frequent (99-80%) HP:0000518
10 splenomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0001744
11 skeletal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002652
12 sensorineural hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000407
13 visual impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000505
14 abnormality of retinal pigmentation 59 32 hallmark (90%) Very frequent (99-80%) HP:0007703
15 ichthyosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008064
16 renal insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0000083
17 retinopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000488
18 intellectual disability, severe 59 32 frequent (33%) Frequent (79-30%) HP:0010864
19 abnormality of metabolism/homeostasis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001939
20 skeletal muscle atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003202
21 hemiplegia/hemiparesis 59 32 hallmark (90%) Very frequent (99-80%) HP:0004374
22 peripheral neuropathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0009830
23 progressive visual loss 59 32 occasional (7.5%) Occasional (29-5%) HP:0000529
24 dry skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0000958
25 cardiomyopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001638
26 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
27 nyctalopia 59 32 frequent (33%) Frequent (79-30%) HP:0000662
28 heart block 59 32 occasional (7.5%) Occasional (29-5%) HP:0012722
29 microphthalmia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000568
30 nail dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002164
31 short metacarpal 59 32 frequent (33%) Frequent (79-30%) HP:0010049
32 anosmia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000458
33 miosis 59 32 frequent (33%) Frequent (79-30%) HP:0000616
34 hammertoe 59 32 frequent (33%) Frequent (79-30%) HP:0001765
35 abnormality of eye movement 59 Frequent (79-30%)
36 abnormality of the eye 59 Very frequent (99-80%)
37 abnormality of vision 59 Very frequent (99-80%)
38 cardiomegaly 32 HP:0001640
39 arrhythmia 32 HP:0011675
40 abnormal renal physiology 32 occasional (7.5%) HP:0012211
41 congestive heart failure 32 HP:0001635
42 abnormality of the foot 59 Very frequent (99-80%)
43 hyporeflexia 32 HP:0001265
44 sensorimotor neuropathy 32 HP:0007141
45 rod-cone dystrophy 32 HP:0000510
46 limb muscle weakness 32 HP:0003690
47 sensory impairment 32 HP:0003474
48 increased csf protein 32 HP:0002922
49 multiple epiphyseal dysplasia 32 HP:0002654
50 retinal degeneration 32 HP:0000546

MGI Mouse Phenotypes related to Refsum Disease, Classic:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.81 AMACR CAT GNPAT HSD17B4 PEX5 PEX7
2 liver/biliary system MP:0005370 9.43 SCP2 AMACR HSD17B4 PEX5 PEX7 PHYH
3 reproductive system MP:0005389 9.1 GNPAT HSD17B4 PEX5 PEX7 PHYH TTPA

Drugs & Therapeutics for Refsum Disease, Classic

Drugs for Refsum Disease, Classic (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 33)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Betaine Approved, Nutraceutical Phase 3 107-43-7 247
2 Bile Acids and Salts Phase 3,Not Applicable
3 Cholic Acids Phase 3,Not Applicable
4 Gastrointestinal Agents Phase 3,Not Applicable
5 Liver Extracts Phase 3
6 Antimetabolites Phase 3,Phase 2
7 Hypolipidemic Agents Phase 3
8 Lipid Regulating Agents Phase 3
9
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
10
alemtuzumab Approved, Investigational Phase 2 216503-57-0
11
Busulfan Approved, Investigational Phase 2 55-98-1 2478
12
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
13
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
14
rituximab Approved Phase 2 174722-31-7 10201696
15
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
16
Tocopherol Approved, Investigational, Nutraceutical Phase 2 1406-66-2 14986
17
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
18 Alkylating Agents Phase 2
19 Antilymphocyte Serum Phase 2
20 Antimetabolites, Antineoplastic Phase 2
21 Antineoplastic Agents, Alkylating Phase 2
22 Immunosuppressive Agents Phase 2
23 N-monoacetylcystine Phase 2
24 Thioctic Acid Phase 2
25 Tocopherols Phase 2
26 Tocotrienols Phase 2
27 Vitamins Phase 2
28 Alpha-lipoic Acid Nutraceutical Phase 2
29 Tocotrienol Investigational, Nutraceutical Phase 2 6829-55-6
30
chenodeoxycholic acid Approved Not Applicable 474-25-9 10133
31
Ursodeoxycholic acid Approved, Investigational Not Applicable 128-13-2 31401
32 Cathartics Not Applicable
33 Laxatives Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid Completed NCT00007020 Phase 3 Cholic Acids
2 Betaine and Peroxisome Biogenesis Disorders Completed NCT01838941 Phase 3 Betaine
3 MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)
4 Inherited Retinal Degenerative Disease Registry Recruiting NCT02435940
5 Study of Bile Acids in Patients With Peroxisomal Disorders Terminated NCT00004442 Not Applicable chenodeoxycholic acid;cholic acid;ursodiol

Search NIH Clinical Center for Refsum Disease, Classic

Cochrane evidence based reviews: refsum disease

Genetic Tests for Refsum Disease, Classic

Genetic tests related to Refsum Disease, Classic:

# Genetic test Affiliating Genes
1 Refsum Disease, Adult, 1 29
2 Phytanic Acid Storage Disease 29 PEX7 PHYH

Anatomical Context for Refsum Disease, Classic

MalaCards organs/tissues related to Refsum Disease, Classic:

41
Skin, Bone, Eye, Heart, Liver, Brain, Retina

Publications for Refsum Disease, Classic

Articles related to Refsum Disease, Classic:

(show top 50) (show all 78)
# Title Authors Year
1
Histologic and ultrastructural features in early and advanced phases of Zellweger spectrum disorder (infantile Refsum disease). ( 29482424 )
2018
2
Phytanic acid attenuates insulin-like growth factor-1 activity via nitric oxide-mediated I^-secretase activation in rat aortic smooth muscle cells: possible implications for pathogenesis of infantile Refsum disease. ( 27886192 )
2017
3
Living-Donor Liver Transplantation From a Heterozygous Parent for Infantile Refsum Disease. ( 27221287 )
2016
4
Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease. ( 26799636 )
2016
5
Brain Lipotoxicity of Phytanic Acid and Very Long-chain Fatty Acids. Harmful Cellular/Mitochondrial Activities in Refsum Disease and X-Linked Adrenoleukodystrophy. ( 27114847 )
2016
6
Conventional and advanced MR imaging in infantile Refsum disease. ( 26701952 )
2015
7
Audiological findings in Infantile Refsum disease. ( 26055198 )
2015
8
Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels. ( 26303611 )
2015
9
Refsum Disease Presenting with a Late-Onset Leukodystrophy. ( 25604618 )
2015
10
Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar bodies and stratum corneum barrier lipid organization. ( 24920240 )
2014
11
Infantile refsum disease in a young adult: case presentation and brief review. ( 25372210 )
2014
12
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
13
Phytanic acid disturbs mitochondrial homeostasis in heart of young rats: a possible pathomechanism of cardiomyopathy in Refsum disease. ( 22527938 )
2012
14
A child with night blindness: preventing serious symptoms of Refsum disease. ( 22156782 )
2012
15
Medical-dental findings and management of a child with infantile Refsum disease: a case report. ( 22591434 )
2012
16
Infantile refsum disease with enamel defects: a case report. ( 21703082 )
2011
17
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
18
Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. ( 20850855 )
2010
19
The effectiveness of long-term dietary therapy in the treatment of adult Refsum disease. ( 20547622 )
2010
20
The influence of the branched-chain fatty acids pristanic acid and Refsum disease-associated phytanic acid on mitochondrial functions and calcium regulation of hippocampal neurons, astrocytes, and oligodendrocytes. ( 19703563 )
2009
21
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
22
Midlife diagnosis of Refsum disease in siblings with retinitis pigmentosa -- the footprint is the clue: a case report. ( 18336720 )
2008
23
Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. ( 19004801 )
2008
24
Phenotype of adult Refsum disease due to a defect in peroxin 7. ( 17325280 )
2007
25
Mechanism of toxicity of the branched-chain fatty acid phytanic acid, a marker of Refsum disease, in astrocytes involves mitochondrial impairment. ( 16386870 )
2006
26
Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid. ( 16737698 )
2006
27
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
28
Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease. ( 16186124 )
2005
29
Orthotopic liver transplantation from a living-related donor in an infant with a peroxisome biogenesis defect of the infantile Refsum disease type. ( 15902563 )
2005
30
Infantile Refsum disease: serial evaluation with MRI. ( 15480616 )
2005
31
Omega-hydroxylation of phytanic acid in rat liver microsomes: implications for Refsum disease. ( 15102880 )
2004
32
Molecular basis of Refsum disease: sequence variations in phytanoyl- CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). ( 14974078 )
2004
33
Changes underlying arrhythmia in the transgenic heart overexpressing Refsum disease gene-associated protein. ( 14672712 )
2004
34
Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease. ( 12700346 )
2003
35
Identification of PEX7 as the second gene involved in Refsum disease. ( 12522768 )
2003
36
Infantile refsum disease: case report. ( 14625237 )
2003
37
Further studies on the substrate spectrum of phytanoyl-CoA hydroxylase: implications for Refsum disease? ( 12923223 )
2003
38
Identification of PEX7 as the second gene involved in Refsum disease. ( 14713215 )
2003
39
Postnatal expression and distribution of Refsum disease gene associated protein in the rat retina and visual cortex: effect of binocular visual deprivation. ( 12034140 )
2002
40
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
41
Refsum disease, peroxisomes and phytanic acid oxidation: a review. ( 11706932 )
2001
42
Cardiac Characteristics of Transgenic Mice Overexpressing Refsum Disease Gene-Associated Protein within the Heart. ( 11527414 )
2001
43
Identification of a brain specific protein that associates with a Refsum disease gene product, phytanoyl-CoA alpha-hydroxylase. ( 10686344 )
2000
44
Infantile refsum disease in four Amish sibs. ( 10607947 )
2000
45
Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution. ( 10632109 )
2000
46
Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated protein. ( 10051602 )
1999
47
Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria. ( 10471774 )
1999
48
Transport of phytanic acid on lipoproteins in Refsum disease. ( 10070615 )
1999
49
Phytanoyl-CoA hydroxylase deficiency. Enzymological and molecular basis of classical Refsum disease. ( 10709665 )
1999
50
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

Variations for Refsum Disease, Classic

UniProtKB/Swiss-Prot genetic disease variations for Refsum Disease, Classic:

75 (show all 14)
# Symbol AA change Variation ID SNP ID
1 PHYH p.Asn269His VAR_005525 rs104894179
2 PHYH p.Arg275Trp VAR_005526 rs104894178
3 PHYH p.Pro173Ser VAR_017483
4 PHYH p.Gln176Lys VAR_017484 rs28939672
5 PHYH p.Asp177Gly VAR_017485 rs770262329
6 PHYH p.Trp193Arg VAR_017486
7 PHYH p.Glu197Gln VAR_017487
8 PHYH p.Ile199Phe VAR_017488
9 PHYH p.Gly204Ser VAR_017489 rs104894173
10 PHYH p.His220Tyr VAR_017490 rs767216891
11 PHYH p.Phe257Ser VAR_017492
12 PHYH p.Arg275Gln VAR_017493 rs104894174
13 PHYH p.Asn83Tyr VAR_018619
14 PHYH p.His175Arg VAR_018631

ClinVar genetic disease variations for Refsum Disease, Classic:

6
(show top 50) (show all 137)
# Gene Variation Type Significance SNP ID Assembly Location
1 PHYH NM_006214.3(PHYH): c.823C> T (p.Arg275Trp) single nucleotide variant Pathogenic rs104894178 GRCh37 Chromosome 10, 13325695: 13325695
2 PHYH NM_006214.3(PHYH): c.823C> T (p.Arg275Trp) single nucleotide variant Pathogenic rs104894178 GRCh38 Chromosome 10, 13283695: 13283695
3 PHYH NM_006214.3(PHYH): c.135-2A> G single nucleotide variant Pathogenic rs201578674 GRCh37 Chromosome 10, 13337608: 13337608
4 PHYH NM_006214.3(PHYH): c.135-2A> G single nucleotide variant Pathogenic rs201578674 GRCh38 Chromosome 10, 13295608: 13295608
5 PHYH NM_006214.3(PHYH): c.164delT (p.Leu55Argfs) deletion Pathogenic rs730882058 GRCh37 Chromosome 10, 13337577: 13337577
6 PHYH NM_006214.3(PHYH): c.164delT (p.Leu55Argfs) deletion Pathogenic rs730882058 GRCh38 Chromosome 10, 13295577: 13295577
7 PHYH NM_006214.3(PHYH): c.805A> C (p.Asn269His) single nucleotide variant Pathogenic rs104894179 GRCh37 Chromosome 10, 13325713: 13325713
8 PHYH NM_006214.3(PHYH): c.805A> C (p.Asn269His) single nucleotide variant Pathogenic rs104894179 GRCh38 Chromosome 10, 13283713: 13283713
9 PHYH PHYH, 3-BP INS, 576GCC insertion Pathogenic
10 PHYH NM_006214.3(PHYH): c.526C> A (p.Gln176Lys) single nucleotide variant Pathogenic rs28939672 GRCh37 Chromosome 10, 13330512: 13330512
11 PHYH NM_006214.3(PHYH): c.526C> A (p.Gln176Lys) single nucleotide variant Pathogenic rs28939672 GRCh38 Chromosome 10, 13288512: 13288512
12 PHYH NM_006214.3(PHYH): c.610G> A (p.Gly204Ser) single nucleotide variant Pathogenic rs104894173 GRCh37 Chromosome 10, 13330428: 13330428
13 PHYH NM_006214.3(PHYH): c.610G> A (p.Gly204Ser) single nucleotide variant Pathogenic rs104894173 GRCh38 Chromosome 10, 13288428: 13288428
14 PHYH NM_006214.3(PHYH): c.824G> A (p.Arg275Gln) single nucleotide variant Pathogenic rs104894174 GRCh37 Chromosome 10, 13325694: 13325694
15 PHYH NM_006214.3(PHYH): c.824G> A (p.Arg275Gln) single nucleotide variant Pathogenic rs104894174 GRCh38 Chromosome 10, 13283694: 13283694
16 PEX7 NM_000288.3(PEX7): c.875T> A (p.Leu292Ter) single nucleotide variant Pathogenic rs1805137 GRCh37 Chromosome 6, 137219351: 137219351
17 PEX7 NM_000288.3(PEX7): c.875T> A (p.Leu292Ter) single nucleotide variant Pathogenic rs1805137 GRCh38 Chromosome 6, 136898213: 136898213
18 PEX7 NM_000288.3(PEX7): c.-45C> T single nucleotide variant Pathogenic rs267608252 GRCh37 Chromosome 6, 137143759: 137143759
19 PEX7 NM_000288.3(PEX7): c.-45C> T single nucleotide variant Pathogenic rs267608252 GRCh38 Chromosome 6, 136822621: 136822621
20 PHYH NM_001037537.1(PHYH): c.417C> T (p.Tyr139=) single nucleotide variant Likely benign rs142720126 GRCh37 Chromosome 10, 13325801: 13325801
21 PHYH NM_001037537.1(PHYH): c.417C> T (p.Tyr139=) single nucleotide variant Likely benign rs142720126 GRCh38 Chromosome 10, 13283801: 13283801
22 PEX7 NM_000288.3(PEX7): c.576C> T (p.Ile192=) single nucleotide variant Uncertain significance rs776411851 GRCh37 Chromosome 6, 137187814: 137187814
23 PEX7 NM_000288.3(PEX7): c.576C> T (p.Ile192=) single nucleotide variant Uncertain significance rs776411851 GRCh38 Chromosome 6, 136866676: 136866676
24 PHYH NM_006214.3(PHYH): c.766_767delGT (p.Val256Phefs) deletion Likely pathogenic rs797045100 GRCh37 Chromosome 10, 13325751: 13325752
25 PHYH NM_006214.3(PHYH): c.766_767delGT (p.Val256Phefs) deletion Likely pathogenic rs797045100 GRCh38 Chromosome 10, 13283751: 13283752
26 PEX7 NM_000288.3(PEX7): c.-31G> A single nucleotide variant Benign/Likely benign rs115866467 GRCh38 Chromosome 6, 136822635: 136822635
27 PEX7 NM_000288.3(PEX7): c.-31G> A single nucleotide variant Benign/Likely benign rs115866467 GRCh37 Chromosome 6, 137143773: 137143773
28 PEX7 NM_000288.3(PEX7): c.-91G> A single nucleotide variant Uncertain significance rs772358439 GRCh37 Chromosome 6, 137143713: 137143713
29 PEX7 NM_000288.3(PEX7): c.-91G> A single nucleotide variant Uncertain significance rs772358439 GRCh38 Chromosome 6, 136822575: 136822575
30 PEX7 NM_000288.3(PEX7): c.-77T> C single nucleotide variant Uncertain significance rs1321472 GRCh37 Chromosome 6, 137143727: 137143727
31 PEX7 NM_000288.3(PEX7): c.-77T> C single nucleotide variant Uncertain significance rs1321472 GRCh38 Chromosome 6, 136822589: 136822589
32 PEX7 NM_000288.3(PEX7): c.-28G> A single nucleotide variant Uncertain significance rs376808803 GRCh37 Chromosome 6, 137143776: 137143776
33 PEX7 NM_000288.3(PEX7): c.-28G> A single nucleotide variant Uncertain significance rs376808803 GRCh38 Chromosome 6, 136822638: 136822638
34 PEX7 NM_000288.3(PEX7): c.188+3A> G single nucleotide variant Uncertain significance rs200234391 GRCh37 Chromosome 6, 137146412: 137146412
35 PEX7 NM_000288.3(PEX7): c.188+3A> G single nucleotide variant Uncertain significance rs200234391 GRCh38 Chromosome 6, 136825274: 136825274
36 PEX7 NM_000288.3(PEX7): c.941A> G (p.Tyr314Cys) single nucleotide variant Uncertain significance rs201106072 GRCh37 Chromosome 6, 137234633: 137234633
37 PEX7 NM_000288.3(PEX7): c.941A> G (p.Tyr314Cys) single nucleotide variant Uncertain significance rs201106072 GRCh38 Chromosome 6, 136913495: 136913495
38 PEX7 NM_000288.3(PEX7): c.*305C> A single nucleotide variant Uncertain significance rs567568009 GRCh37 Chromosome 6, 137234969: 137234969
39 PEX7 NM_000288.3(PEX7): c.*305C> A single nucleotide variant Uncertain significance rs567568009 GRCh38 Chromosome 6, 136913831: 136913831
40 PEX7 NM_000288.3(PEX7): c.*367T> C single nucleotide variant Uncertain significance rs886061124 GRCh37 Chromosome 6, 137235031: 137235031
41 PEX7 NM_000288.3(PEX7): c.*367T> C single nucleotide variant Uncertain significance rs886061124 GRCh38 Chromosome 6, 136913893: 136913893
42 PEX7 NM_000288.3(PEX7): c.94C> T (p.Leu32=) single nucleotide variant Uncertain significance rs886061118 GRCh37 Chromosome 6, 137143897: 137143897
43 PEX7 NM_000288.3(PEX7): c.94C> T (p.Leu32=) single nucleotide variant Uncertain significance rs886061118 GRCh38 Chromosome 6, 136822759: 136822759
44 PEX7 NM_000288.3(PEX7): c.130+11G> T single nucleotide variant Uncertain significance rs886061119 GRCh37 Chromosome 6, 137143944: 137143944
45 PEX7 NM_000288.3(PEX7): c.130+11G> T single nucleotide variant Uncertain significance rs886061119 GRCh38 Chromosome 6, 136822806: 136822806
46 PEX7 NM_000288.3(PEX7): c.130+13C> A single nucleotide variant Uncertain significance rs886061120 GRCh37 Chromosome 6, 137143946: 137143946
47 PEX7 NM_000288.3(PEX7): c.130+13C> A single nucleotide variant Uncertain significance rs886061120 GRCh38 Chromosome 6, 136822808: 136822808
48 PEX7 NM_000288.3(PEX7): c.418-4G> T single nucleotide variant Uncertain significance rs199552223 GRCh37 Chromosome 6, 137167207: 137167207
49 PEX7 NM_000288.3(PEX7): c.418-4G> T single nucleotide variant Uncertain significance rs199552223 GRCh38 Chromosome 6, 136846069: 136846069
50 PEX7 NM_000288.3(PEX7): c.737G> A (p.Arg246Lys) single nucleotide variant Uncertain significance rs780186421 GRCh37 Chromosome 6, 137191131: 137191131

Expression for Refsum Disease, Classic

Search GEO for disease gene expression data for Refsum Disease, Classic.

Pathways for Refsum Disease, Classic

Pathways related to Refsum Disease, Classic according to KEGG:

37
# Name Kegg Source Accession
1 Peroxisome hsa04146

GO Terms for Refsum Disease, Classic

Cellular components related to Refsum Disease, Classic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.86 AMACR CAT GNPAT HSD17B4 PEX5 PHYH
2 peroxisomal membrane GO:0005778 9.63 CAT GNPAT HSD17B4 PEX14 PEX16 PEX5
3 peroxisomal matrix GO:0005782 9.5 AMACR CAT GNPAT HSD17B4 PEX7 PHYH
4 peroxisome GO:0005777 9.32 AMACR CAT GNPAT HSD17B4 PEX14 PEX16

Biological processes related to Refsum Disease, Classic according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.85 AP1S1 PEX14 PEX5 PEX7
2 fatty acid metabolic process GO:0006631 9.67 AMACR GNPAT HSD17B4 PHYH
3 fatty acid beta-oxidation GO:0006635 9.61 HSD17B4 PEX5 PEX7
4 cellular lipid metabolic process GO:0044255 9.54 GNPAT PEX5
5 response to fatty acid GO:0070542 9.52 CAT GNPAT
6 alpha-linolenic acid metabolic process GO:0036109 9.51 HSD17B4 SCP2
7 protein targeting to peroxisome GO:0006625 9.49 PEX16 PEX7
8 protein import into peroxisome membrane GO:0045046 9.48 PEX16 PEX5
9 ether lipid biosynthetic process GO:0008611 9.46 GNPAT PEX7
10 bile acid biosynthetic process GO:0006699 9.43 AMACR HSD17B4 SCP2
11 protein import into peroxisome matrix, docking GO:0016560 9.4 PEX14 PEX5
12 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.33 AMACR HSD17B4 SCP2
13 negative regulation of protein homotetramerization GO:1901094 9.32 PEX14 PEX5
14 protein import into peroxisome matrix GO:0016558 9.26 PEX14 PEX16 PEX5 PEX7
15 peroxisome organization GO:0007031 9.02 PEX14 PEX16 PEX5 PEX7 SCP2

Molecular functions related to Refsum Disease, Classic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 9.1 AMACR CAT GNPAT HSD17B4 PEX14 SCP2

Sources for Refsum Disease, Classic

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
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74 UMLS via Orphanet
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