RD
MCID: RFS006
MIFTS: 63

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 57
Refsum Disease 57 12 73 25 20 43 53 58 72 36 13 54 44 15 39 70 32
Heredopathia Atactica Polyneuritiformis 57 12 20 43 53 58 72
Phytanic Acid Oxidase Deficiency 57 73 20 72
Phytanic Acid Storage Disease 43 53 29 6
Hmsn Iv 57 43 58 72
Refsum Disease, Adult, 1 57 29 6
Adult Refsum Disease 25 43 58
Refsum's Disease 12 43 72
Refsum Syndrome 25 43 6
Hereditary Motor and Sensory Neuropathy Type Iv 43 58
Hereditary Motor and Sensory Neuropathy Iv 57 72
Classic Refsum Disease 43 58
Hmsn Type Iv 12 43
Hmsn 4 20 58
Hmsn4 57 72
Hereditary Motor and Sensory Neuropathy Iv; Hmsn4 57
Hereditary Sensory and Motor Neuropathy Type 4 20
Hereditary Motor and Sensory Neuropathy Type 4 58
Phytanic-Coa Hydroxylase Deficiency 58
Hypertrophic Neuropathy of Refsum 20
Disorder of Cornification 11 20
Hsmn Iv 12
Doc 11 20
Crd 43
Ard 43
Rd 72

Characteristics:

Orphanet epidemiological data:

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

OMIM®:

57 (Updated 05-Apr-2021)
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

MedlinePlus Genetics : 43 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 zellweger spectrum disorder and peroxisome biogenesis disorder 1a. 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 Liver Extracts and Acetylcysteine have been mentioned in the context of this disorder. Affiliated tissues include eye, retina and heart, and related phenotypes are abnormal pyramidal sign and ataxia

GARD : 20 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® : 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) (Updated 05-Apr-2021)

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 : 72 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 : 73 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 199)
# Related Disease Score Top Affiliating Genes
1 zellweger spectrum disorder 31.2 PEX6 PEX5 PEX3 PEX26 PEX16 PEX14
2 peroxisome biogenesis disorder 1a 31.2 PEX6 PEX5 PEX3 PEX26 PEX16 PEX14
3 chronic polyneuropathy 31.0 PHYH PEX7
4 leukodystrophy 30.5 SCP2 PEX6 PEX5 PEX3 PEX26 PEX16
5 rhizomelic chondrodysplasia punctata, type 1 30.2 SCP2 PHYH PEX7 PEX6 PEX5 HSD17B4
6 sensorineural hearing loss 30.0 PEX6 PEX5 PEX26 PEX12 PEX10 PEX1
7 chondrodysplasia punctata syndrome 29.7 PHYH PEX7 PEX6 PEX5 PEX26 PEX16
8 alpha-methylacyl-coa racemase deficiency 29.6 SCP2 PEX6 PEX16 PEX11B HSD17B4 HACL1
9 fundus dystrophy 29.6 PHYH PEX7 PEX6 PEX3 PEX26 PEX12
10 neonatal adrenoleukodystrophy 29.4 PEX6 PEX5 PEX3 PEX26 PEX16 PEX14
11 adrenoleukodystrophy 29.3 SCP2 PEX7 PEX6 PEX5 PEX3 PEX26
12 peroxisomal disease 29.1 SCP2 PHYH PEX7 PEX6 PEX5 PEX3
13 rhizomelic chondrodysplasia punctata 28.9 SCP2 PHYH PEX7 PEX6 PEX5 PEX3
14 peroxisome biogenesis disorder 1b 28.6 SCP2 PHYH PEX7 PEX6 PEX5 PEX3
15 zellweger syndrome 28.5 SCP2 PHYH PEX7 PEX6 PEX5 PEX3
16 chylomicron retention disease 11.5
17 cone-rod dystrophy 2 11.5
18 spondylometaphyseal dysplasia with cone-rod dystrophy 11.5
19 cortisone reductase deficiency 11.2
20 refsum disease with increased pipecolic acidemia 11.2
21 cortisone reductase deficiency 1 11.1
22 hereditary motor and sensory neuropathy v 11.1
23 goiter, multinodular, cystic renal disease, and digital anomalies 11.1
24 peroxisome biogenesis disorder 2b 11.1
25 peroxisome biogenesis disorder 3b 11.1
26 peroxisome biogenesis disorder 4b 11.1
27 peroxisome biogenesis disorder 5b 11.1
28 peroxisome biogenesis disorder 6b 11.1
29 peroxisome biogenesis disorder 7b 11.1
30 peroxisome biogenesis disorder 11b 11.1
31 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 11.0
32 pseudovaginal perineoscrotal hypospadias 11.0
33 flynn-aird syndrome 10.9
34 peroxisome biogenesis disorder 2a 10.9
35 peroxisome biogenesis disorder 3a 10.9
36 peroxisome biogenesis disorder 4a 10.9
37 peroxisome biogenesis disorder 5a 10.9
38 peroxisome biogenesis disorder 6a 10.9
39 peroxisome biogenesis disorder 7a 10.9
40 peroxisome biogenesis disorder 8a 10.9
41 peroxisome biogenesis disorder 8b 10.9
42 peroxisome biogenesis disorder 10a 10.9
43 peroxisome biogenesis disorder 11a 10.9
44 peroxisome biogenesis disorder 12a 10.9
45 peroxisome biogenesis disorder 13a 10.9
46 rud syndrome 10.9
47 polyneuropathy 10.6
48 ichthyosis 10.6
49 ataxia and polyneuropathy, adult-onset 10.4
50 yemenite deaf-blind hypopigmentation syndrome 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

Human phenotypes related to Refsum Disease, Classic:

58 31 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
2 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
3 cataract 58 31 hallmark (90%) Very frequent (99-80%) HP:0000518
4 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
5 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
6 abnormality of retinal pigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007703
7 ichthyosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008064
8 retinopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000488
9 dry skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000958
10 hemiplegia/hemiparesis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004374
11 anosmia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000458
12 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
13 abnormality of metabolism/homeostasis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001939
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 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
17 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
18 splenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001744
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 abnormality of epiphysis morphology 58 31 frequent (33%) Frequent (79-30%) HP:0005930
22 nyctalopia 58 31 frequent (33%) Frequent (79-30%) HP:0000662
23 short metacarpal 58 31 frequent (33%) Frequent (79-30%) HP:0010049
24 miosis 58 31 frequent (33%) Frequent (79-30%) HP:0000616
25 hammertoe 58 31 frequent (33%) Frequent (79-30%) HP:0001765
26 hypotonia 31 frequent (33%) HP:0001252
27 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
28 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
29 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083
30 progressive visual loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0000529
31 microphthalmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000568
32 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
33 heart block 58 31 occasional (7.5%) Occasional (29-5%) HP:0012722
34 abnormal renal physiology 31 occasional (7.5%) HP:0012211
35 abnormality of eye movement 58 Frequent (79-30%)
36 muscular hypotonia 58 Frequent (79-30%)
37 visual impairment 58 Frequent (79-30%)
38 cardiomegaly 31 HP:0001640
39 congestive heart failure 31 HP:0001635
40 arrhythmia 31 HP:0011675
41 abnormality of the eye 58 Very frequent (99-80%)
42 abnormality of vision 58 Very frequent (99-80%)
43 abnormality of the foot 58 Very frequent (99-80%)
44 hyporeflexia 31 HP:0001265
45 rod-cone dystrophy 31 HP:0000510
46 limb muscle weakness 31 HP:0003690
47 sensory impairment 31 HP:0003474
48 retinal degeneration 31 HP:0000546
49 multiple epiphyseal dysplasia 31 HP:0002654
50 elevated levels of phytanic acid 31 HP:0010571

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
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 (Updated 05-Apr-2021)

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 HACL1 PEX3 PHYHIP
3 Decreased viability GR00381-A-1 9.5 GNPAT PHYH
4 Decreased viability GR00386-A-1 9.5 PEX16 PEX26
5 Decreased viability GR00402-S-2 9.5 HACL1 PEX10 PEX12 PEX26 PEX7

MGI Mouse Phenotypes related to Refsum Disease, Classic:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10 ALDH3A2 GNPAT HSD17B4 PEX1 PEX10 PEX11B
2 growth/size/body region MP:0005378 9.97 AMACR GNPAT HACL1 HSD17B4 PEX1 PEX10
3 homeostasis/metabolism MP:0005376 9.83 ALDH3A2 AMACR CAT GNPAT HACL1 HSD17B4
4 liver/biliary system MP:0005370 9.23 AMACR HSD17B4 PEX1 PEX11B PEX5 PEX7

Drugs & Therapeutics for Refsum Disease, Classic

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

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

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 Completed NCT00007020 Phase 3 Cholic Acids
2 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)
3 A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J) Recruiting NCT03810508
4 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
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
Eye, Retina, Heart, Liver, Skeletal Muscle, Brain, Skin

Publications for Refsum Disease, Classic

Articles related to Refsum Disease, Classic:

(show top 50) (show all 326)
# Title Authors PMID Year
1
Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). 61 54 25 57 6
14974078 2004
2
Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease. 6 25 57 54
10767344 2000
3
Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. 6 25 57
12325024 2002
4
Identification of PAHX, a Refsum disease gene. 61 6 57 54
9326939 1997
5
Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. 61 6 57 54
9326940 1997
6
Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation. 57 25 6
2433405 1987
7
Phenotype of adult Refsum disease due to a defect in peroxin 7. 6 54 25 61
17325280 2007
8
Identification of PEX7 as the second gene involved in Refsum disease. 6 61 54 25
12522768 2003
9
A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation. 61 25 57
8413964 1993
10
Non-manifesting Refsum heterozygotes carrying the c.135-2A>G PAHX gene transition. 6 61 54
18612766 2008
11
Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. 25 6
11781871 2002
12
Structure-function analysis of phytanoyl-CoA 2-hydroxylase mutations causing Refsum's disease. 6 25
11555634 2001
13
Identification of genetic heterogeneity in Refsum's disease. 54 57
10951529 2000
14
Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution. 54 25 61
10632109 2000
15
Localization of Refsum disease with increased pipecolic acidaemia to chromosome 10p by homozygosity mapping and carrier testing in a single nuclear family. 57 61
8595422 1995
16
Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years. 57 61
2452736 1988
17
Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease. 57 61
6160883 1980
18
Congenital heart defects common in rhizomelic chondrodysplasia punctata. 6
26408048 2016
19
Rhizomelic Chondrodysplasia Punctata Type 1 Caused by a Novel Mutation in the PEX7 Gene. 6
25800479 2015
20
Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1. 6
26587300 2015
21
Rhizomelic chondrodysplasia punctata and cardiac pathology. 6
23572185 2013
22
Functional characterization of novel mutations in GNPAT and AGPS, causing rhizomelic chondrodysplasia punctata (RCDP) types 2 and 3. 6
21990100 2012
23
In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor. 6
22008564 2011
24
Phytanic acid metabolism in health and disease. 61 25
21683154 2011
25
Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. 25 61
20850855 2010
26
Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease. 25 61
12700346 2003
27
Identification of PEX7 as the second gene involved in Refsum disease. 25 61
14713215 2003
28
Refsum's disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation. 54 25
11948235 2002
29
Intracellular localization, function, and dysfunction of the peroxisome-targeting signal type 2 receptor, Pex7p, in mammalian cells. 6
11756410 2002
30
Refsum disease, peroxisomes and phytanic acid oxidation: a review. 25 61
11706932 2001
31
Rhizomelic Chondrodysplasia Punctata Type 1 6
20301447 2001
32
Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. 25 61
10655068 2000
33
Transport of phytanic acid on lipoproteins in Refsum disease. 61 25
10070615 1999
34
A novel nonsense mutation of the PEX7 gene in a patient with rhizomelic chondrodysplasia punctata. 6
10083738 1999
35
A mobile PTS2 receptor for peroxisomal protein import in Pichia pastoris. 6
9472033 1998
36
Phytanoyl-coenzyme A hydroxylase deficiency -- the enzyme defect in Refsum's disease. 57
9221344 1997
37
Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. 6
9090381 1997
38
Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor. 6
9090383 1997
39
Rhizomelic chondrodysplasia punctata is a peroxisomal protein targeting disease caused by a non-functional PTS2 receptor. 6
9090382 1997
40
Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes. 57
7918611 1994
41
Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients. 61 25
1282471 1992
42
Refsum's disease revealed by cardiac disorders. 57
2466186 1989
43
Patterns of Refsum's disease. Phytanic acid oxidase deficiency. 57
6201142 1984
44
Phytanic acid storage disease: hearing maintained after 15 years of dietary treatment. 57
6185882 1983
45
Metabolism of phytanic acid in Refsum's disease. 57
6172683 1982
46
Heredopathia atactica polyneuritiformis phytanic-acid storage disease, Refsum's disease:" a biochemically well-defined disease with a specific dietary treatment. 57
6170281 1981
47
Heredopathia atactica polyneuritiformis (refsum's disease) treated by diet and plasma-exchange. 57
85164 1979
48
Phytanic acid in patients with Refsum's syndrome and response to dietary treatment. 57
4188898 1970
49
Refsum's disease: defective oxidation of phytanic acid in tissue cultures derived from homozygotes and heterozygotes. 57
4188238 1969
50
Localization of the oxidative defect in phytanic acid degradation in patients with Refsum's disease. 57
4181594 1969

Variations for Refsum Disease, Classic

ClinVar genetic disease variations for Refsum Disease, Classic:

6 (show top 50) (show all 166)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PHYH NM_006214.4(PHYH):c.164del (p.Leu55fs) Deletion Pathogenic 7583 rs730882058 GRCh37: 10:13337577-13337577
GRCh38: 10:13295577-13295577
2 PHYH NM_006214.4(PHYH):c.805A>C (p.Asn269His) SNV Pathogenic 7584 rs104894179 GRCh37: 10:13325713-13325713
GRCh38: 10:13283713-13283713
3 PHYH PHYH, 3-BP INS, 576GCC Insertion Pathogenic 7585 GRCh37:
GRCh38:
4 PHYH NM_006214.4(PHYH):c.526C>A (p.Gln176Lys) SNV Pathogenic 7586 rs28939672 GRCh37: 10:13330512-13330512
GRCh38: 10:13288512-13288512
5 PHYH NM_006214.4(PHYH):c.610G>A (p.Gly204Ser) SNV Pathogenic 7587 rs104894173 GRCh37: 10:13330428-13330428
GRCh38: 10:13288428-13288428
6 PHYH NM_006214.4(PHYH):c.824G>A (p.Arg275Gln) SNV Pathogenic 7588 rs104894174 GRCh37: 10:13325694-13325694
GRCh38: 10:13283694-13283694
7 PHYH NM_006214.4(PHYH):c.135-1G>C SNV Pathogenic 812375 rs1057272016 GRCh37: 10:13337607-13337607
GRCh38: 10:13295607-13295607
8 PEX7 NM_000288.4(PEX7):c.-45C>T SNV Pathogenic 38871 rs267608252 GRCh37: 6:137143759-137143759
GRCh38: 6:136822621-136822621
9 PEX7 NM_000288.4(PEX7):c.6_12TGCGGTG[3] (p.Gly7fs) Microsatellite Pathogenic 370629 rs62636519 GRCh37: 6:137143807-137143808
GRCh38: 6:136822669-136822670
10 PEX7 NM_000288.4(PEX7):c.40A>C (p.Thr14Pro) SNV Pathogenic 7790 rs61753233 GRCh37: 6:137143843-137143843
GRCh38: 6:136822705-136822705
11 PEX7 NM_000288.4(PEX7):c.45_52dup (p.His18fs) Duplication Pathogenic 7784 rs63535662 GRCh37: 6:137143840-137143841
GRCh38: 6:136822702-136822703
12 PEX7 NM_000288.4(PEX7):c.130+1G>A SNV Pathogenic 639671 rs267608253 GRCh37: 6:137143934-137143934
GRCh38: 6:136822796-136822796
13 PEX7 NM_000288.4(PEX7):c.429del (p.Val144fs) Deletion Pathogenic 554785 rs61753248 GRCh37: 6:137167222-137167222
GRCh38: 6:136846084-136846084
14 PEX7 NM_000288.4(PEX7):c.183del (p.Phe61fs) Deletion Pathogenic 225436 rs774131564 GRCh37: 6:137146400-137146400
GRCh38: 6:136825262-136825262
15 PEX7 NM_000288.4(PEX7):c.49_70dup (p.Phe24fs) Duplication Pathogenic 846733 GRCh37: 6:137143851-137143852
GRCh38: 6:136822713-136822714
16 PEX7 NM_000288.4(PEX7):c.592C>T (p.Gln198Ter) SNV Pathogenic 813366 rs764924345 GRCh37: 6:137187830-137187830
GRCh38: 6:136866692-136866692
17 PEX7 NM_000288.4(PEX7):c.345T>G (p.Tyr115Ter) SNV Pathogenic 7786 rs121909154 GRCh37: 6:137166758-137166758
GRCh38: 6:136845620-136845620
18 PEX7 NM_000288.4(PEX7):c.120C>G (p.Tyr40Ter) SNV Pathogenic 7788 rs61753238 GRCh37: 6:137143923-137143923
GRCh38: 6:136822785-136822785
19 PEX7 NM_000288.4(PEX7):c.653C>T (p.Ala218Val) SNV Pathogenic 7781 rs121909151 GRCh37: 6:137191047-137191047
GRCh38: 6:136869909-136869909
20 PEX7 NM_000288.4(PEX7):c.120C>G (p.Tyr40Ter) SNV Pathogenic 7788 rs61753238 GRCh37: 6:137143923-137143923
GRCh38: 6:136822785-136822785
21 PHYH NM_006214.4(PHYH):c.823C>T (p.Arg275Trp) SNV Pathogenic 7580 rs104894178 GRCh37: 10:13325695-13325695
GRCh38: 10:13283695-13283695
22 PEX7 NM_000288.4(PEX7):c.649G>A (p.Gly217Arg) SNV Pathogenic 7782 rs121909152 GRCh37: 6:137191043-137191043
GRCh38: 6:136869905-136869905
23 PHYH NM_006214.4(PHYH):c.135-2A>G SNV Pathogenic 7581 rs201578674 GRCh37: 10:13337608-13337608
GRCh38: 10:13295608-13295608
24 PEX7 NM_000288.4(PEX7):c.340-10A>G SNV Pathogenic 7787 rs267608255 GRCh37: 6:137166743-137166743
GRCh38: 6:136845605-136845605
25 PEX7 NM_000288.4(PEX7):c.694C>T (p.Arg232Ter) SNV Pathogenic 7783 rs121909153 GRCh37: 6:137191088-137191088
GRCh38: 6:136869950-136869950
26 PEX7 NM_000288.4(PEX7):c.903+1G>C SNV Pathogenic 7785 rs148591292 GRCh37: 6:137219380-137219380
GRCh38: 6:136898242-136898242
27 PEX7 NM_000288.4(PEX7):c.875T>A (p.Leu292Ter) SNV Pathogenic 7780 rs1805137 GRCh37: 6:137219351-137219351
GRCh38: 6:136898213-136898213
28 PEX7 NM_000288.4(PEX7):c.875T>A (p.Leu292Ter) SNV Pathogenic 7780 rs1805137 GRCh37: 6:137219351-137219351
GRCh38: 6:136898213-136898213
29 PEX7 NM_000288.4(PEX7):c.875T>A (p.Leu292Ter) SNV Pathogenic 7780 rs1805137 GRCh37: 6:137219351-137219351
GRCh38: 6:136898213-136898213
30 PHYH NM_006214.4(PHYH):c.679-1dup Duplication Pathogenic 1034255 GRCh37: 10:13325834-13325835
GRCh38: 10:13283834-13283835
31 PEX7 NM_000288.4(PEX7):c.188+1G>C SNV Pathogenic/Likely pathogenic 188975 rs267608254 GRCh37: 6:137146410-137146410
GRCh38: 6:136825272-136825272
32 PHYH NM_006214.4(PHYH):c.823C>T (p.Arg275Trp) SNV Pathogenic/Likely pathogenic 7580 rs104894178 GRCh37: 10:13325695-13325695
GRCh38: 10:13283695-13283695
33 PHYH NM_006214.4(PHYH):c.135-2A>G SNV Pathogenic/Likely pathogenic 7581 rs201578674 GRCh37: 10:13337608-13337608
GRCh38: 10:13295608-13295608
34 PEX7 NM_000288.4(PEX7):c.418-1G>C SNV Likely pathogenic 843768 GRCh37: 6:137167210-137167210
GRCh38: 6:136846072-136846072
35 PEX7 NM_000288.4(PEX7):c.183del (p.Phe61fs) Deletion Likely pathogenic 225436 rs774131564 GRCh37: 6:137146400-137146400
GRCh38: 6:136825262-136825262
36 PEX7 NM_000288.4(PEX7):c.736_747+17del Deletion Likely pathogenic 371420 rs1057517257 GRCh37: 6:137191128-137191156
GRCh38: 6:136869990-136870018
37 PEX7 NM_000288.4(PEX7):c.363_526+230del Deletion Likely pathogenic 659636 rs1582744649 GRCh37: 6:137166776-137167549
GRCh38: 6:136845638-136846411
38 PHYH NM_006214.4(PHYH):c.766_767del (p.Val256fs) Deletion Likely pathogenic 208603 rs797045100 GRCh37: 10:13325751-13325752
GRCh38: 10:13283751-13283752
39 PHYH NM_006214.4(PHYH):c.414+2T>C SNV Likely pathogenic 558590 rs1554784939 GRCh37: 10:13336426-13336426
GRCh38: 10:13294426-13294426
40 PEX7 NM_000288.4(PEX7):c.94C>T (p.Leu32=) SNV Conflicting interpretations of pathogenicity 355526 rs886061118 GRCh37: 6:137143897-137143897
GRCh38: 6:136822759-136822759
41 PHYH NM_006214.4(PHYH):c.734G>A (p.Arg245Gln) SNV Conflicting interpretations of pathogenicity 198539 rs62619919 GRCh37: 10:13325784-13325784
GRCh38: 10:13283784-13283784
42 PEX7 NM_000288.4(PEX7):c.615C>T (p.Asp205=) SNV Conflicting interpretations of pathogenicity 355532 rs147298444 GRCh37: 6:137187853-137187853
GRCh38: 6:136866715-136866715
43 PEX7 NM_000288.4(PEX7):c.903+8A>G SNV Conflicting interpretations of pathogenicity 795513 rs779919482 GRCh37: 6:137219387-137219387
GRCh38: 6:136898249-136898249
44 PEX7 NM_000288.4(PEX7):c.418-4G>T SNV Conflicting interpretations of pathogenicity 355531 rs199552223 GRCh37: 6:137167207-137167207
GRCh38: 6:136846069-136846069
45 PEX7 NM_000288.4(PEX7):c.290C>G (p.Thr97Ser) SNV Uncertain significance 1028672 GRCh37: 6:137147558-137147558
GRCh38: 6:136826420-136826420
46 PEX7 NM_000288.4(PEX7):c.701C>T (p.Pro234Leu) SNV Uncertain significance 1038000 GRCh37: 6:137191095-137191095
GRCh38: 6:136869957-136869957
47 PEX7 NM_000288.4(PEX7):c.418-3T>C SNV Uncertain significance 1039835 GRCh37: 6:137167208-137167208
GRCh38: 6:136846070-136846070
48 PEX7 NM_000288.4(PEX7):c.193G>A (p.Asp65Asn) SNV Uncertain significance 1041978 GRCh37: 6:137147461-137147461
GRCh38: 6:136826323-136826323
49 PEX7 NM_000288.4(PEX7):c.629A>G (p.Asn210Ser) SNV Uncertain significance 1042208 GRCh37: 6:137187867-137187867
GRCh38: 6:136866729-136866729
50 PEX7 NM_000288.4(PEX7):c.917C>T (p.Ser306Phe) SNV Uncertain significance 1043826 GRCh37: 6:137234609-137234609
GRCh38: 6:136913471-136913471

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

72 (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 10.35 SCP2 PEX6 PEX5 PEX3 PEX26 PEX16
2 cytosol GO:0005829 10.21 SCP2 PHYH PEX7 PEX6 PEX5 PEX3
3 mitochondrion GO:0005739 10 SCP2 PHYH PEX5 PEX11B GNPAT CAT
4 intracellular membrane-bounded organelle GO:0043231 9.88 SCP2 PEX11B HACL1 CAT AMACR ALDH3A2
5 protein-containing complex GO:0032991 9.85 SCP2 PEX5 PEX3 PEX14 PEX11B CAT
6 peroxisomal membrane GO:0005778 9.83 PEX7 PEX6 PEX5 PEX3 PEX26 PEX16
7 peroxisomal matrix GO:0005782 9.81 SCP2 PHYH PEX7 PEX5 HSD17B4 HACL1
8 integral component of peroxisomal membrane GO:0005779 9.73 PEX3 PEX26 PEX16 PEX12 PEX11B PEX10
9 peroxisome GO:0005777 9.6 SCP2 PHYH PEX7 PEX6 PEX5 PEX3
10 peroxisomal importomer complex GO:1990429 9.32 PEX14 PEX12

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

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.97 PEX7 PEX5 PEX26 PEX14 PEX1
2 fatty acid metabolic process GO:0006631 9.85 PHYH HSD17B4 HACL1 GNPAT AMACR ALDH3A2
3 protein import into peroxisome matrix GO:0016558 9.81 PEX7 PEX6 PEX5 PEX26 PEX16 PEX14
4 fatty acid beta-oxidation GO:0006635 9.73 SCP2 PEX7 PEX5 HSD17B4
5 peroxisome organization GO:0007031 9.7 SCP2 PEX7 PEX6 PEX5 PEX3 PEX16
6 bile acid biosynthetic process GO:0006699 9.65 SCP2 HSD17B4 AMACR
7 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.63 SCP2 HSD17B4 AMACR
8 response to fatty acid GO:0070542 9.59 GNPAT CAT
9 cellular lipid metabolic process GO:0044255 9.58 PEX5 GNPAT
10 very long-chain fatty acid metabolic process GO:0000038 9.58 PEX5 HSD17B4
11 fatty acid alpha-oxidation GO:0001561 9.58 PHYH HACL1 ALDH3A2
12 bile acid metabolic process GO:0008206 9.56 SCP2 AMACR
13 protein import into peroxisome membrane GO:0045046 9.56 PEX5 PEX3 PEX26 PEX16
14 alpha-linolenic acid metabolic process GO:0036109 9.55 SCP2 HSD17B4
15 ether lipid biosynthetic process GO:0008611 9.54 PEX7 GNPAT
16 protein targeting to peroxisome GO:0006625 9.53 SCP2 PHYH PEX7 PEX6 PEX5 PEX26
17 protein import into peroxisome matrix, docking GO:0016560 9.52 PEX5 PEX14
18 peroxisome membrane biogenesis GO:0016557 9.51 PEX3 PEX16
19 protein import into peroxisome matrix, translocation GO:0016561 9.5 PEX6 PEX5 PEX14
20 methyl-branched fatty acid metabolic process GO:0097089 9.49 PHYH HACL1

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 9.65 PEX7 PEX11B HSD17B4 CAT ALDH3A2
2 catalytic activity GO:0003824 9.55 SCP2 PHYH HACL1 GNPAT AMACR
3 protein C-terminus binding GO:0008022 9.17 PEX6 PEX5 PEX26 PEX16 PEX12 PEX10
4 peroxisome targeting sequence binding GO:0000268 8.96 PEX5 CAT

Sources for Refsum Disease, Classic

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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