RD
MCID: RFS006
MIFTS: 64

Refsum Disease, Classic (RD)

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

Aliases & Classifications for Refsum Disease, Classic

MalaCards integrated aliases for Refsum Disease, Classic:

Name: Refsum Disease, Classic 56
Refsum Disease 56 12 74 24 52 25 53 58 73 36 13 54 43 15 39 71 32
Heredopathia Atactica Polyneuritiformis 56 12 52 25 53 58 73
Phytanic Acid Oxidase Deficiency 56 74 52 73
Phytanic Acid Storage Disease 25 53 29 6
Hmsn Iv 56 25 58 73
Refsum Disease, Adult, 1 56 29 6
Adult Refsum Disease 24 25 58
Refsum's Disease 12 25 73
Refsum Syndrome 24 25 6
Hereditary Motor and Sensory Neuropathy Type Iv 25 58
Hereditary Motor and Sensory Neuropathy Iv 56 73
Classic Refsum Disease 25 58
Hmsn Type Iv 12 25
Hmsn 4 52 58
Hmsn4 56 73
Hereditary Motor and Sensory Neuropathy Iv; Hmsn4 56
Hereditary Sensory and Motor Neuropathy Type 4 52
Hereditary Motor and Sensory Neuropathy Type 4 58
Phytanic-Coa Hydroxylase Deficiency 58
Hypertrophic Neuropathy of Refsum 52
Disorder of Cornification 11 52
Hsmn Iv 12
Doc 11 52
Crd 25
Ard 25
Rd 73

Characteristics:

Orphanet epidemiological data:

58
refsum disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy;

OMIM:

56
Inheritance:
autosomal recessive

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


HPO:

31
refsum disease, classic:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare skin diseases
Inborn errors of metabolism


Summaries for Refsum Disease, Classic

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. The vision loss associated with Refsum disease is caused by an eye disorder called retinitis pigmentosa. This disorder affects the retina, the light-sensitive layer at the back of the eye. Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. The first sign of retinitis pigmentosa is usually a loss of night vision, which often becomes apparent in childhood. Over a period of years, the disease disrupts side (peripheral) vision and may eventually lead to blindness. Vision loss and anosmia are seen in almost everyone with Refsum disease, but other signs and symptoms vary. About one-third of affected individuals are born with bone abnormalities of the hands and feet. Features that appear later in life can include progressive muscle weakness and wasting; poor balance and coordination (ataxia); hearing loss; and dry, scaly skin (ichthyosis). Additionally, some people with Refsum disease develop an abnormal heart rhythm (arrhythmia) and related heart problems that can be life-threatening.

MalaCards based summary : Refsum Disease, Classic, also known as refsum disease, is related to peroxisome biogenesis disorder 1b and zellweger spectrum disorder. 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 Gastrointestinal Agents have been mentioned in the context of this disorder. Affiliated tissues include skin, heart and bone, and related phenotypes are cataract and skeletal dysplasia

NIH Rare Diseases : 52 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.

OMIM : 56 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)

NINDS : 53 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.

KEGG : 36 Refsum disease (RD) is an autosomal recessive sensory motor neuropathy charactarized by retinitis pigmentosa, peripheral neuropathy, anosmia, deafness, cerebellar ataxia and elevated protein concentrations in the cerebrospinal fluid in the absence of an increased number of cells. The age at which symptoms first present in RD can be variable although most cases present in adolescence. Because the patients are unable to metabolize phytanic acid derived from exogenous sources, highly raised plasma phytanic acid (PA) level in tissues and body fluids is the hallmark of RD. Mutant forms of phytanoyl-CoA 2-hydroxylase (PHYH) which plays a key role of phytanic acid alpha-oxidation in peroxisomes have been shown to be responsible for some, but not all, cases of Refsum's disease. Peroxisomal PHYH import occurs via PEX7 which is the peroxisomal matrix protein receptor. Though PEX7 has been identified another responsible gene, there still remain a small number of patients in whom no mutations in either of these two genes can be found.

UniProtKB/Swiss-Prot : 73 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.

Wikipedia : 74 Refsum disease is an autosomal recessive neurological disease that results in the over-accumulation of... 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 681)
# Related Disease Score Top Affiliating Genes
1 peroxisome biogenesis disorder 1b 31.6 SCP2 PHYH PEX7 PEX5 PEX3 PEX26
2 zellweger spectrum disorder 31.5 PEX5 PEX3 PEX26 PEX2 PEX16 PEX14
3 chronic polyneuropathy 31.5 PHYH PEX7
4 ichthyosis 31.3 PHYH PEX7 GNPAT ALDH3A2
5 peroxisome biogenesis disorder 1a 31.1 PEX5 PEX3 PEX26 PEX2 PEX16 PEX14
6 leukodystrophy 30.7 SCP2 PEX5 PEX3 PEX26 PEX2 PEX16
7 alpha-methylacyl-coa racemase deficiency 30.4 SCP2 HSD17B4 AMACR
8 fundus dystrophy 30.1 PHYH PEX7 PEX3 PEX26 PEX16 PEX12
9 rhizomelic chondrodysplasia punctata, type 1 30.0 SCP2 PHYH PEX7 PEX5 HSD17B4 GNPAT
10 chondrodysplasia punctata syndrome 29.6 PHYH PEX7 PEX5 PEX26 PEX2 PEX16
11 cataract 29.5 PEX7 PEX5 PEX11B GNPAT CAT
12 sensorineural hearing loss 29.1 PEX26 PEX12 PEX10 PEX1
13 adrenoleukodystrophy 28.7 SCP2 PEX7 PEX5 PEX3 PEX26 PEX2
14 neonatal adrenoleukodystrophy 28.6 SCP2 PEX7 PEX5 PEX3 PEX26 PEX2
15 peroxisomal disease 28.6 SCP2 PHYH PEX7 PEX5 PEX3 PEX26
16 rhizomelic chondrodysplasia punctata 28.3 SCP2 PHYH PEX7 PEX5 PEX3 PEX26
17 zellweger syndrome 28.0 SCP2 PHYH PEX7 PEX5 PEX3 PEX26
18 peroxisomal biogenesis disorder 27.9 SCP2 PHYH PEX7 PEX5 PEX3 PEX26
19 refsum disease with increased pipecolic acidemia 12.4
20 respiratory distress syndrome in premature infants 12.3
21 chylomicron retention disease 12.1
22 spondylometaphyseal dysplasia with cone-rod dystrophy 12.0
23 restrictive dermopathy, lethal 12.0
24 reticular dysgenesis 12.0
25 cortisone reductase deficiency 11.8
26 radin blood group antigen 11.7
27 respiratory distress syndrome, infant 11.7
28 adult acute respiratory distress syndrome 11.6
29 bronchopulmonary dysplasia 11.5
30 choroidal dystrophy, central areolar, 1 11.5
31 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 11.4
32 cortisone reductase deficiency 1 11.4
33 cortisone reductase deficiency 2 11.4
34 hereditary motor and sensory neuropathy v 11.4
35 goiter, multinodular, cystic renal disease, and digital anomalies 11.4
36 staphylococcal toxic shock syndrome 11.2
37 peroxisome biogenesis disorder 2b 11.2
38 peroxisome biogenesis disorder 3b 11.2
39 peroxisome biogenesis disorder 4b 11.2
40 peroxisome biogenesis disorder 5b 11.2
41 peroxisome biogenesis disorder 6b 11.2
42 peroxisome biogenesis disorder 7b 11.2
43 peroxisome biogenesis disorder 11b 11.2
44 adult respiratory distress syndrome 11.2
45 renal hypodysplasia/aplasia 1 11.2
46 renal hypodysplasia/aplasia 2 11.2
47 surfactant dysfunction 11.2
48 flynn-aird syndrome 11.1
49 peroxisome biogenesis disorder 2a 11.1
50 peroxisome biogenesis disorder 3a 11.1

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



Diseases related to Refsum Disease, Classic

Symptoms & Phenotypes for Refsum Disease, Classic

Human phenotypes related to Refsum Disease, Classic:

58 31 (show top 50) (show all 52)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cataract 58 31 hallmark (90%) Very frequent (99-80%) HP:0000518
2 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
3 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
4 abnormality of retinal pigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007703
5 ichthyosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008064
6 retinopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000488
7 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
8 abnormality of metabolism/homeostasis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001939
9 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
10 hemiplegia/hemiparesis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004374
11 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
12 dry skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000958
13 anosmia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000458
14 nail dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002164
15 cardiomyopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001638
16 splenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001744
17 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
18 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
19 intellectual disability, severe 58 31 frequent (33%) Frequent (79-30%) HP:0010864
20 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
21 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
22 abnormality of epiphysis morphology 58 31 frequent (33%) Frequent (79-30%) HP:0005930
23 nyctalopia 58 31 frequent (33%) Frequent (79-30%) HP:0000662
24 short metacarpal 58 31 frequent (33%) Frequent (79-30%) HP:0010049
25 miosis 58 31 frequent (33%) Frequent (79-30%) HP:0000616
26 hammertoe 58 31 frequent (33%) Frequent (79-30%) HP:0001765
27 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083
28 progressive visual loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0000529
29 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
30 heart block 58 31 occasional (7.5%) Occasional (29-5%) HP:0012722
31 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
32 microphthalmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000568
33 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
34 abnormal renal physiology 31 occasional (7.5%) HP:0012211
35 visual impairment 58 Frequent (79-30%)
36 cardiomegaly 31 HP:0001640
37 arrhythmia 31 HP:0011675
38 congestive heart failure 31 HP:0001635
39 abnormality of eye movement 58 Frequent (79-30%)
40 abnormality of the eye 58 Very frequent (99-80%)
41 abnormality of vision 58 Very frequent (99-80%)
42 abnormality of the foot 58 Very frequent (99-80%)
43 hyporeflexia 31 HP:0001265
44 rod-cone dystrophy 31 HP:0000510
45 sensory impairment 31 HP:0003474
46 retinal degeneration 31 HP:0000546
47 multiple epiphyseal dysplasia 31 HP:0002654
48 elevated levels of phytanic acid 31 HP:0010571
49 sensorimotor neuropathy 31 HP:0007141
50 limb muscle weakness 31 HP:0003690

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
ichthyosis

Head And Neck Nose:
anosmia

Neurologic Peripheral Nervous System:
hyporeflexia
sensory impairment
limb weakness
peripheral sensorimotor neuropathy
limb atrophy
more
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

Skeletal Feet:
pes cavus
shortening of the metatarsals

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

GenomeRNAi Phenotypes related to Refsum Disease, Classic according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00240-S-1 9.5 PEX16 PEX26
2 Decreased viability GR00249-S 9.5 AMACR PEX3 PHYHIP
3 Decreased viability GR00381-A-1 9.5 GNPAT PHYH
4 Decreased viability GR00386-A-1 9.5 PEX16 PEX26 TTPA
5 Decreased viability GR00402-S-2 9.5 PEX10 PEX12 PEX2 PEX26 PEX7

MGI Mouse Phenotypes related to Refsum Disease, Classic:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.16 ALDH3A2 AMACR CAT GNPAT HSD17B4 PEX1
2 behavior/neurological MP:0005386 10.15 ALDH3A2 GNPAT HSD17B4 PEX1 PEX10 PEX11B
3 growth/size/body region MP:0005378 10.1 AMACR GNPAT HSD17B4 PEX1 PEX10 PEX11B
4 liver/biliary system MP:0005370 9.81 AMACR HSD17B4 PEX1 PEX11B PEX2 PEX5
5 mortality/aging MP:0010768 9.73 AMACR CAT GNPAT HSD17B4 PEX1 PEX10
6 nervous system MP:0003631 9.36 ALDH3A2 GNPAT HSD17B4 PEX1 PEX10 PEX11B

Drugs & Therapeutics for Refsum Disease, Classic

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

(show all 29)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Betaine Approved, Nutraceutical Phase 3 107-43-7 247
2 Gastrointestinal Agents Phase 3
3 Cholic Acids Phase 3
4 Bile Acids and Salts Phase 3
5 Liver Extracts Phase 3
6 Hypolipidemic Agents Phase 3
7 Lipid Regulating Agents Phase 3
8 Antimetabolites Phase 3
9
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
10
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
11
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
12
rituximab Approved Phase 2 174722-31-7 10201696
13
Tocopherol Approved, Investigational Phase 2 1406-66-2, 54-28-4 14986
14
Busulfan Approved, Investigational Phase 2 55-98-1 2478
15
alemtuzumab Approved, Investigational Phase 2 216503-57-0
16
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
17
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
18 Tocotrienol Investigational Phase 2 6829-55-6
19 Alpha-lipoic Acid Phase 2
20 Vitamins Phase 2
21 Thioctic Acid Phase 2
22 Tocopherols Phase 2
23 Tocotrienols Phase 2
24 N-monoacetylcystine Phase 2
25 Antilymphocyte Serum Phase 2
26
chenodeoxycholic acid Approved 474-25-9 10133
27
Ursodeoxycholic acid Approved, Investigational 128-13-2 31401
28 Laxatives
29 Cathartics

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Investigation in the Pathogenesis of Liver Disease in Patients With Inborn Errors of Bile Acid Metabolism." This Study Was Previously Registered by the NCRR and Identified as NCRR-M01RR08084-0009 Completed NCT00007020 Phase 3 Cholic Acids
2 A Pilot, Open Label Trial Assessing the Safety and Efficacy of Betaine in Children With Peroxisome Biogenesis Disorders. Completed NCT01838941 Phase 3 Betaine
3 MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG 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 A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J) Recruiting NCT03810508
5 Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD) Recruiting NCT01668186
6 Foundation Fighting Blindness Registry, My Retina Tracker Recruiting NCT02435940
7 Study of Bile Acids in Patients With Peroxisomal Disorders Terminated NCT00004442 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:

40
Skin, Heart, Bone, Eye, Retina, Liver, Brain

Publications for Refsum Disease, Classic

Articles related to Refsum Disease, Classic:

(show top 50) (show all 312)
# Title Authors PMID Year
1
Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease. 54 6 56 24
10767344 2000
2
Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. 24 56 6
12325024 2002
3
Identification of PAHX, a Refsum disease gene. 54 61 56 6
9326939 1997
4
Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. 54 61 6 56
9326940 1997
5
Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation. 56 24 6
2433405 1987
6
Phenotype of adult Refsum disease due to a defect in peroxin 7. 61 54 24 6
17325280 2007
7
Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). 56 24 61 54
14974078 2004
8
Identification of PEX7 as the second gene involved in Refsum disease. 24 54 6 61
12522768 2003
9
A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation. 24 56 61
8413964 1993
10
Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. 24 6
11781871 2002
11
Refsum Disease 6 61
20301527 2006
12
Identification of genetic heterogeneity in Refsum's disease. 56 54
10951529 2000
13
Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution. 61 54 24
10632109 2000
14
Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family. 61 56
8595422 1995
15
Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years. 56 61
2452736 1988
16
Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease. 61 56
6160883 1980
17
Phytanic acid metabolism in health and disease. 61 24
21683154 2011
18
Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. 24 61
20850855 2010
19
Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease. 24 61
12700346 2003
20
Identification of PEX7 as the second gene involved in Refsum disease. 61 24
14713215 2003
21
Refsum's disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation. 54 24
11948235 2002
22
Refsum disease, peroxisomes and phytanic acid oxidation: a review. 24 61
11706932 2001
23
Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. 24 61
10655068 2000
24
Transport of phytanic acid on lipoproteins in Refsum disease. 61 24
10070615 1999
25
Phytanoyl-coenzyme A hydroxylase deficiency -- the enzyme defect in Refsum's disease. 56
9221344 1997
26
Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. 6
9090381 1997
27
Rhizomelic chondrodysplasia punctata is a peroxisomal protein targeting disease caused by a non-functional PTS2 receptor. 6
9090382 1997
28
Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes. 56
7918611 1994
29
Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients. 24 61
1282471 1992
30
Refsum's disease revealed by cardiac disorders. 56
2466186 1989
31
Patterns of Refsum's disease. Phytanic acid oxidase deficiency. 56
6201142 1984
32
Phytanic acid storage disease: hearing maintained after 15 years of dietary treatment. 56
6185882 1983
33
Metabolism of phytanic acid in Refsum's disease. 56
6172683 1982
34
Heredopathia atactica polyneuritiformis phytanic-acid storage disease, Refsum's disease:" a biochemically well-defined disease with a specific dietary treatment. 56
6170281 1981
35
Heredopathia atactica polyneuritiformis (refsum's disease) treated by diet and plasma-exchange. 56
85164 1979
36
Phytanic acid in patients with Refsum's syndrome and response to dietary treatment. 56
4188898 1970
37
Refsum's disease: defective oxidation of phytanic acid in tissue cultures derived from homozygotes and heterozygotes. 56
4188238 1969
38
Refsum's disease: characterization of the enzyme defect in cell culture. 56
4181593 1969
39
Localization of the oxidative defect in phytanic acid degradation in patients with Refsum's disease. 56
4181594 1969
40
Refsum's disease: nature of the enzyme defect. 56
4180573 1967
41
Studies on the metabolic error in Refsum's disease. 56
4164676 1967
42
Refsum's disease--a recently characterized lipidosis involving the nervous system. Combined clinical staff conference at the National Institutes of Health. 56
4163283 1967
43
Conversion of H3-phytol to phytanic acid and its incorporation into plasma lipid fractions in heredopathia atactica polyneuritiformis. 56
4166674 1966
44
Dietary effects on serum-phytanic-acid levels and on clinical manifestations in heredopathia atactica polyneuritiformis. 56
4159604 1966
45
REFSUM'S DISEASE (HEREDOPATHIA ATACTICA POLYNEURITIFORMIS): AN INBORN ERROR OF LIPID METABOLISM WITH STORAGE OF 3,7,11,15-TETRAMETHYL HEXADECANOIC ACID. I. REPORT OF A CASE. 56
14320689 1965
46
[ON THE PRESENCE OF 3,7,11,15-TETRAMETHYLHEXADECANOIC ACID (PHYTANIC ACID) IN THE CHOLESTEROL ESTERS AND OTHER LIPOID FRACTIONS OF THE ORGANS IN A CASE OF A DISEASE OF UNKNOWN ORIGIN (POSSIBLY HEREDOPATHIA ATACTICA POLYNEURITIFORMIS, REFSUM'S SYNDROME)]. 56
14058273 1963
47
Refsum's syndrome affecting a brother and two sisters. 56
13560885 1958
48
Heredopathia atactica polyneuritiformis. 56
13045168 1952
49
Heredopathia Atactica Polyneuritiformis (Refsum's Syndrome). 56
19993784 1951
50
Heredopathia atactica polyneuritiformis in children. 56
18140089 1949

Variations for Refsum Disease, Classic

ClinVar genetic disease variations for Refsum Disease, Classic:

6 (show top 50) (show all 71) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PHYH NM_006214.4(PHYH):c.135-1G>CSNV Pathogenic 812375 10:13337607-13337607 10:13295607-13295607
2 PHYH NM_006214.4(PHYH):c.164del (p.Leu55fs)deletion Pathogenic 7583 rs730882058 10:13337577-13337577 10:13295577-13295577
3 PHYH NM_006214.4(PHYH):c.805A>C (p.Asn269His)SNV Pathogenic 7584 rs104894179 10:13325713-13325713 10:13283713-13283713
4 PHYH PHYH, 3-BP INS, 576GCCinsertion Pathogenic 7585
5 PHYH NM_006214.4(PHYH):c.526C>A (p.Gln176Lys)SNV Pathogenic 7586 rs28939672 10:13330512-13330512 10:13288512-13288512
6 PHYH NM_006214.4(PHYH):c.610G>A (p.Gly204Ser)SNV Pathogenic 7587 rs104894173 10:13330428-13330428 10:13288428-13288428
7 PHYH NM_006214.4(PHYH):c.824G>A (p.Arg275Gln)SNV Pathogenic 7588 rs104894174 10:13325694-13325694 10:13283694-13283694
8 PEX7 NM_000288.4(PEX7):c.875T>A (p.Leu292Ter)SNV Pathogenic 7780 rs1805137 6:137219351-137219351 6:136898213-136898213
9 PEX7 NM_000288.4(PEX7):c.120C>G (p.Tyr40Ter)SNV Pathogenic 7788 rs61753238 6:137143923-137143923 6:136822785-136822785
10 PEX7 NM_000288.4(PEX7):c.-45C>TSNV Pathogenic 38871 rs267608252 6:137143759-137143759 6:136822621-136822621
11 PHYH NM_006214.4(PHYH):c.823C>T (p.Arg275Trp)SNV Pathogenic/Likely pathogenic 7580 rs104894178 10:13325695-13325695 10:13283695-13283695
12 PHYH NM_006214.4(PHYH):c.135-2A>GSNV Pathogenic/Likely pathogenic 7581 rs201578674 10:13337608-13337608 10:13295608-13295608
13 PHYH NM_006214.4(PHYH):c.414+2T>CSNV Likely pathogenic 558590 rs1554784939 10:13336426-13336426 10:13294426-13294426
14 PHYH NM_006214.4(PHYH):c.766_767del (p.Val256fs)deletion Likely pathogenic 208603 rs797045100 10:13325751-13325752 10:13283751-13283752
15 PEX7 NM_000288.4(PEX7):c.377A>C (p.Gln126Pro)SNV Conflicting interpretations of pathogenicity 255746 rs113268723 6:137166790-137166790 6:136845652-136845652
16 PHYH NM_006214.4(PHYH):c.606C>A (p.Asn202Lys)SNV Conflicting interpretations of pathogenicity 299250 rs201979258 10:13330432-13330432 10:13288432-13288432
17 PHYH NM_006214.4(PHYH):c.356C>T (p.Thr119Met)SNV Conflicting interpretations of pathogenicity 299255 rs34571629 10:13336486-13336486 10:13294486-13294486
18 PHYH NM_006214.4(PHYH):c.601C>G (p.Arg201Gly)SNV Conflicting interpretations of pathogenicity 299251 rs143957922 10:13330437-13330437 10:13288437-13288437
19 PHYH NM_006214.4(PHYH):c.792C>T (p.His264=)SNV Conflicting interpretations of pathogenicity 299246 rs372047384 10:13325726-13325726 10:13283726-13283726
20 PHYH NM_006214.4(PHYH):c.1010_1012dup (p.Leu338_Ter339insHis)duplication Conflicting interpretations of pathogenicity 444210 rs566116760 10:13320305-13320306 10:13278305-13278306
21 PEX7 NM_000288.4(PEX7):c.695G>A (p.Arg232Gln)SNV Conflicting interpretations of pathogenicity 500853 rs191969418 6:137191089-137191089 6:136869951-136869951
22 PHYH NM_006214.4(PHYH):c.678+5G>TSNV Conflicting interpretations of pathogenicity 198192 rs201499815 10:13330355-13330355 10:13288355-13288355
23 PHYH NM_006214.4(PHYH):c.734G>A (p.Arg245Gln)SNV Conflicting interpretations of pathogenicity 198539 rs62619919 10:13325784-13325784 10:13283784-13283784
24 PEX7 NM_000288.4(PEX7):c.340-10A>GSNV Conflicting interpretations of pathogenicity 7787 rs267608255 6:137166743-137166743 6:136845605-136845605
25 PHYH NM_006214.4(PHYH):c.354C>G (p.Ile118Met)SNV Uncertain significance 429240 rs779724199 10:13336488-13336488 10:13294488-13294488
26 PEX7 NM_000288.4(PEX7):c.86C>T (p.Pro29Leu)SNV Uncertain significance 498141 rs757852291 6:137143889-137143889 6:136822751-136822751
27 PHYH NM_006214.4(PHYH):c.621_623del (p.Val208del)deletion Uncertain significance 556208 rs755838466 10:13330415-13330417 10:13288415-13288417
28 PHYH NM_006214.4(PHYH):c.1_24dup (p.Met1_Ala8dup)duplication Uncertain significance 555188 rs1554785878 10:13342018-13342019 10:13300018-13300019
29 PHYH NM_006214.4(PHYH):c.703G>A (p.Gly235Arg)SNV Uncertain significance 631628 rs750819521 10:13325815-13325815 10:13283815-13283815
30 PHYH NM_006214.4(PHYH):c.*499C>TSNV Uncertain significance 877811 10:13319802-13319802 10:13277802-13277802
31 PHYH NM_006214.4(PHYH):c.*434A>GSNV Uncertain significance 877812 10:13319867-13319867 10:13277867-13277867
32 PHYH NM_006214.4(PHYH):c.*417A>GSNV Uncertain significance 877813 10:13319884-13319884 10:13277884-13277884
33 PHYH NM_006214.4(PHYH):c.*253G>TSNV Uncertain significance 877814 10:13320048-13320048 10:13278048-13278048
34 PHYH NM_006214.4(PHYH):c.*188A>CSNV Uncertain significance 877815 10:13320113-13320113 10:13278113-13278113
35 PHYH NM_006214.4(PHYH):c.*25C>TSNV Uncertain significance 877978 10:13320276-13320276 10:13278276-13278276
36 PHYH NM_006214.4(PHYH):c.948T>C (p.Asn316=)SNV Uncertain significance 877979 10:13322991-13322991 10:13280991-13280991
37 PHYH NM_006214.4(PHYH):c.739C>T (p.His247Tyr)SNV Uncertain significance 879440 10:13325779-13325779 10:13283779-13283779
38 PHYH NM_006214.4(PHYH):c.679G>T (p.Gly227Trp)SNV Uncertain significance 879441 10:13325839-13325839 10:13283839-13283839
39 PHYH NM_006214.4(PHYH):c.83A>G (p.His28Arg)SNV Uncertain significance 877868 10:13340238-13340238 10:13298238-13298238
40 PHYH NM_006214.4(PHYH):c.828+4A>TSNV Uncertain significance 877980 10:13325686-13325686 10:13283686-13283686
41 PHYH NM_006214.4(PHYH):c.679-11T>ASNV Uncertain significance 299247 rs886046828 10:13325850-13325850 10:13283850-13283850
42 PHYH NM_006214.4(PHYH):c.581C>T (p.Thr194Met)SNV Uncertain significance 299252 rs141554572 10:13330457-13330457 10:13288457-13288457
43 PHYH NM_006214.4(PHYH):c.245G>A (p.Arg82Gln)SNV Uncertain significance 299258 rs886046830 10:13337496-13337496 10:13295496-13295496
44 PHYH NM_006214.4(PHYH):c.-20G>CSNV Uncertain significance 299263 rs546291238 10:13342062-13342062 10:13300062-13300062
45 PHYH NM_006214.4(PHYH):c.829-3C>ASNV Uncertain significance 299245 rs116930123 10:13323113-13323113 10:13281113-13281113
46 PHYH NM_006214.4(PHYH):c.574G>A (p.Ala192Thr)SNV Uncertain significance 299253 rs751660253 10:13330464-13330464 10:13288464-13288464
47 PHYH NM_006214.4(PHYH):c.176A>C (p.Lys59Thr)SNV Uncertain significance 299259 rs886046831 10:13337565-13337565 10:13295565-13295565
48 PHYH NM_001323082.1(PHYH):c.-78G>TSNV Uncertain significance 299264 rs886046832 10:13342120-13342120 10:13300120-13300120
49 PHYH NM_006214.4(PHYH):c.321G>T (p.Ser107=)SNV Uncertain significance 299256 rs115198308 10:13336521-13336521 10:13294521-13294521
50 PHYH NM_006214.4(PHYH):c.1009A>G (p.Asn337Asp)SNV Uncertain significance 299243 rs758218321 10:13320309-13320309 10:13278309-13278309

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

73 (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 rs121156443
12 PHYH p.Arg275Gln VAR_017493 rs104894174
13 PHYH p.Asn83Tyr VAR_018619
14 PHYH p.His175Arg VAR_018631

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:

36
# 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 membrane GO:0016020 10.31 SCP2 PEX5 PEX3 PEX26 PEX2 PEX16
2 mitochondrion GO:0005739 9.95 SCP2 PHYH PEX5 PEX11B GNPAT CAT
3 protein-containing complex GO:0032991 9.85 SCP2 PEX5 PEX3 PEX14 PEX11B CAT
4 peroxisomal membrane GO:0005778 9.83 PEX7 PEX5 PEX3 PEX26 PEX2 PEX16
5 peroxisomal matrix GO:0005782 9.8 SCP2 PHYH PEX7 HSD17B4 GNPAT CAT
6 integral component of peroxisomal membrane GO:0005779 9.63 PEX3 PEX26 PEX2 PEX16 PEX12 PEX11B
7 peroxisome GO:0005777 9.55 SCP2 PHYH PEX7 PEX5 PEX3 PEX26
8 peroxisomal importomer complex GO:1990429 9.32 PEX14 PEX12

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

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.97 PEX7 PEX5 PEX26 PEX14 PEX1
2 protein ubiquitination GO:0016567 9.96 PEX5 PEX2 PEX14 PEX12 PEX10
3 protein import into peroxisome matrix GO:0016558 9.81 PEX7 PEX5 PEX26 PEX2 PEX16 PEX14
4 fatty acid metabolic process GO:0006631 9.8 PHYH HSD17B4 GNPAT AMACR ALDH3A2
5 fatty acid beta-oxidation GO:0006635 9.72 SCP2 PEX7 PEX5 PEX2 HSD17B4
6 peroxisome organization GO:0007031 9.7 SCP2 PEX7 PEX5 PEX3 PEX2 PEX16
7 bile acid biosynthetic process GO:0006699 9.63 SCP2 HSD17B4 AMACR
8 very long-chain fatty acid metabolic process GO:0000038 9.61 PEX5 PEX2 HSD17B4
9 response to fatty acid GO:0070542 9.58 GNPAT CAT
10 cellular lipid metabolic process GO:0044255 9.58 PEX5 GNPAT
11 protein import into peroxisome membrane GO:0045046 9.56 PEX5 PEX3 PEX26 PEX16
12 alpha-linolenic acid metabolic process GO:0036109 9.55 SCP2 HSD17B4
13 bile acid metabolic process GO:0008206 9.54 SCP2 AMACR
14 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.54 SCP2 HSD17B4 AMACR
15 fatty acid alpha-oxidation GO:0001561 9.52 PHYH ALDH3A2
16 ether lipid biosynthetic process GO:0008611 9.51 PEX7 GNPAT
17 protein targeting to peroxisome GO:0006625 9.5 SCP2 PHYH PEX7 PEX5 PEX26 PEX2
18 protein import into peroxisome matrix, docking GO:0016560 9.49 PEX5 PEX14
19 peroxisome membrane biogenesis GO:0016557 9.48 PEX3 PEX16

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

# Name GO ID Score Top Affiliating Genes
1 protein homodimerization activity GO:0042803 9.55 PEX7 PEX11B HSD17B4 CAT ALDH3A2
2 protein C-terminus binding GO:0008022 9.26 PEX26 PEX16 PEX12 PEX1
3 peroxisome targeting sequence binding GO:0000268 8.62 PEX5 CAT

Sources for Refsum Disease, Classic

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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