RD
MCID: RFS006
MIFTS: 62

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 75 24 53 25 54 59 74 37 13 55 44 15 40 72 33
Heredopathia Atactica Polyneuritiformis 57 12 53 25 54 59 74
Phytanic Acid Oxidase Deficiency 57 75 53 74
Phytanic Acid Storage Disease 25 54 29 6
Hmsn Iv 57 25 59 74
Refsum Disease, Adult, 1 57 29 6
Adult Refsum Disease 24 25 59
Refsum's Disease 12 25 74
Hereditary Motor and Sensory Neuropathy Type Iv 25 59
Hereditary Motor and Sensory Neuropathy Iv 57 74
Classic Refsum Disease 25 59
Refsum Syndrome 24 25
Hmsn Type Iv 12 25
Hmsn 4 53 59
Hmsn4 57 74
Hereditary Motor and Sensory Neuropathy Iv; Hmsn4 57
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 74

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:



External Ids:

Disease Ontology 12 DOID:10582
OMIM 57 266500
KEGG 37 H00075
ICD9CM 35 356.3
MeSH 44 D012035
NCIt 50 C85043
SNOMED-CT 68 25362006
ICD10 33 G60.1
MESH via Orphanet 45 D012035
ICD10 via Orphanet 34 G60.1
UMLS via Orphanet 73 C0034960
Orphanet 59 ORPHA773
UMLS 72 C0034960

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 rhizomelic chondrodysplasia punctata and chondrodysplasia punctata syndrome. 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 ataxia and abnormal pyramidal sign

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.

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)

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.

KEGG : 37
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 : 74 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 : 75 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 655)
# Related Disease Score Top Affiliating Genes
1 rhizomelic chondrodysplasia punctata 30.7 PHYH PEX7 GNPAT
2 chondrodysplasia punctata syndrome 30.6 PEX7 GNPAT
3 zellweger syndrome 29.9 PEX14 PEX1 GNPAT
4 peroxisomal disease 29.6 PHYH PEX7 PEX1 HSD17B4 GNPAT CAT
5 rhizomelic chondrodysplasia punctata, type 1 29.3 SCP2 PHYH PEX7 HSD17B4 GNPAT
6 neonatal adrenoleukodystrophy 29.3 SCP2 PEX7 PEX14 PEX1 CAT
7 alpha-methylacyl-coa racemase deficiency 29.0 SCP2 PHYH HSD17B4 HACL1 AMACR
8 peroxisome biogenesis disorder 1b 28.6 PHYH PEX7 PEX14 PEX1 HSD17B4 GNPAT
9 refsum disease with increased pipecolic acidemia 12.4
10 respiratory distress syndrome in premature infants 12.3
11 chylomicron retention disease 12.1
12 spondylometaphyseal dysplasia with cone-rod dystrophy 12.0
13 reticular dysgenesis 12.0
14 restrictive dermopathy, lethal 11.8
15 cortisone reductase deficiency 11.7
16 radin blood group antigen 11.7
17 zellweger spectrum disorder 11.7
18 respiratory distress syndrome, infant 11.7
19 adult acute respiratory distress syndrome 11.6
20 bronchopulmonary dysplasia 11.5
21 choroidal dystrophy, central areolar, 1 11.5
22 cortisone reductase deficiency 1 11.4
23 cortisone reductase deficiency 2 11.4
24 hereditary motor and sensory neuropathy v 11.4
25 leukodystrophy 11.4
26 peroxisome biogenesis disorder-zellweger syndrome spectrum 11.4
27 peroxisome biogenesis disorder 1a 11.3
28 peroxisome biogenesis disorder 2b 11.2
29 peroxisome biogenesis disorder 3b 11.2
30 peroxisome biogenesis disorder 4b 11.2
31 peroxisome biogenesis disorder 5b 11.2
32 peroxisome biogenesis disorder 6b 11.2
33 peroxisome biogenesis disorder 7b 11.2
34 peroxisome biogenesis disorder 11b 11.2
35 staphylococcal toxic shock syndrome 11.2
36 goiter, multinodular, cystic renal disease, and digital anomalies 11.2
37 daneman davy mancer syndrome 11.2
38 adult respiratory distress syndrome 11.2
39 renal hypodysplasia/aplasia 1 11.2
40 renal hypodysplasia/aplasia 2 11.2
41 flynn-aird syndrome 11.1
42 peroxisome biogenesis disorder 2a 11.1
43 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 11.1
44 peroxisome biogenesis disorder 3a 11.1
45 peroxisome biogenesis disorder 4a 11.1
46 peroxisome biogenesis disorder 5a 11.1
47 peroxisome biogenesis disorder 6a 11.1
48 peroxisome biogenesis disorder 7a 11.1
49 peroxisome biogenesis disorder 8a 11.1
50 peroxisome biogenesis disorder 8b 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:

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

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin:
ichthyosis

Skeletal Feet:
pes cavus
shortening of the metatarsals

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

Head And Neck Nose:
anosmia

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

MGI Mouse Phenotypes related to Refsum Disease, Classic:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.61 AMACR CAT CRAT GNPAT HSD17B4 PEX1
2 liver/biliary system MP:0005370 9.1 AMACR HSD17B4 PEX1 PEX7 PHYH SCP2

Drugs & Therapeutics for Refsum Disease, Classic

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

(show all 34)
# 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 Antimetabolites Phase 3
7 Lipid Regulating Agents Phase 3
8 Hypolipidemic Agents Phase 3
9
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
10
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
11
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
12
alemtuzumab Approved, Investigational Phase 2 216503-57-0
13
rituximab Approved Phase 2 174722-31-7 10201696
14
Tocopherol Approved, Investigational Phase 2 1406-66-2, 54-28-4 14986
15
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
16
Busulfan Approved, Investigational Phase 2 55-98-1 2478
17
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
18 Tocotrienol Investigational Phase 2 6829-55-6
19 Alkylating Agents Phase 2
20 Tocotrienols Phase 2
21 Alpha-lipoic Acid Phase 2
22 Antilymphocyte Serum Phase 2
23 Tocopherols Phase 2
24 N-monoacetylcystine Phase 2
25 Immunosuppressive Agents Phase 2
26 Vitamins Phase 2
27 Thioctic Acid Phase 2
28 Immunologic Factors Phase 2
29 Antimetabolites, Antineoplastic Phase 2
30 Antineoplastic Agents, Alkylating Phase 2
31
chenodeoxycholic acid Approved 474-25-9 10133
32
Ursodeoxycholic acid Approved, Investigational 128-13-2 31401
33 Cathartics
34 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." 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 Foundation Fighting Blindness Registry, My Retina Tracker Recruiting NCT02435940
6 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 PHYH

Anatomical Context for Refsum Disease, Classic

MalaCards organs/tissues related to Refsum Disease, Classic:

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

Publications for Refsum Disease, Classic

Articles related to Refsum Disease, Classic:

(show top 50) (show all 308)
# Title Authors PMID Year
1
Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease. 9 4 8 71
10767344 2000
2
Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. 4 8 71
12325024 2002
3
Identification of PAHX, a Refsum disease gene. 9 38 8 71
9326939 1997
4
Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. 9 38 8 71
9326940 1997
5
Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation. 4 8 71
2433405 1987
6
Phenotype of adult Refsum disease due to a defect in peroxin 7. 9 38 4 71
17325280 2007
7
Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). 9 38 4 8
14974078 2004
8
Identification of PEX7 as the second gene involved in Refsum disease. 9 38 4 71
12522768 2003
9
A new peroxisomal disease with impaired phytanic and pipecolic acid oxidation. 38 4 8
8413964 1993
10
Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. 4 71
11781871 2002
11
Refsum Disease 38 71
20301527 2006
12
Identification of genetic heterogeneity in Refsum's disease. 9 8
10951529 2000
13
Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution. 9 38 4
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. 38 8
8595422 1995
15
Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years. 38 8
2452736 1988
16
Therapeutic trial of plasmapheresis in Refsum disease and in Fabry disease. 38 8
6160883 1980
17
Phytanic acid metabolism in health and disease. 38 4
21683154 2011
18
Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. 38 4
20850855 2010
19
Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease. 38 4
12700346 2003
20
Identification of PEX7 as the second gene involved in Refsum disease. 38 4
14713215 2003
21
Refsum's disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation. 9 4
11948235 2002
22
Refsum disease, peroxisomes and phytanic acid oxidation: a review. 38 4
11706932 2001
23
Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. 38 4
10655068 2000
24
Transport of phytanic acid on lipoproteins in Refsum disease. 38 4
10070615 1999
25
Phytanoyl-coenzyme A hydroxylase deficiency -- the enzyme defect in Refsum's disease. 8
9221344 1997
26
Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. 71
9090381 1997
27
Rhizomelic chondrodysplasia punctata is a peroxisomal protein targeting disease caused by a non-functional PTS2 receptor. 71
9090382 1997
28
Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes. 8
7918611 1994
29
Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients. 38 4
1282471 1992
30
Refsum's disease revealed by cardiac disorders. 8
2466186 1989
31
Patterns of Refsum's disease. Phytanic acid oxidase deficiency. 8
6201142 1984
32
Phytanic acid storage disease: hearing maintained after 15 years of dietary treatment. 8
6185882 1983
33
Metabolism of phytanic acid in Refsum's disease. 8
6172683 1982
34
Heredopathia atactica polyneuritiformis phytanic-acid storage disease, Refsum's disease:" a biochemically well-defined disease with a specific dietary treatment. 8
6170281 1981
35
Heredopathia atactica polyneuritiformis (refsum's disease) treated by diet and plasma-exchange. 8
85164 1979
36
Phytanic acid in patients with Refsum's syndrome and response to dietary treatment. 8
4188898 1970
37
Refsum's disease: defective oxidation of phytanic acid in tissue cultures derived from homozygotes and heterozygotes. 8
4188238 1969
38
Refsum's disease: characterization of the enzyme defect in cell culture. 8
4181593 1969
39
Localization of the oxidative defect in phytanic acid degradation in patients with Refsum's disease. 8
4181594 1969
40
Refsum's disease: nature of the enzyme defect. 8
4180573 1967
41
Studies on the metabolic error in Refsum's disease. 8
4164676 1967
42
Refsum's disease--a recently characterized lipidosis involving the nervous system. Combined clinical staff conference at the National Institutes of Health. 8
4163283 1967
43
Conversion of H3-phytol to phytanic acid and its incorporation into plasma lipid fractions in heredopathia atactica polyneuritiformis. 8
4166674 1966
44
Dietary effects on serum-phytanic-acid levels and on clinical manifestations in heredopathia atactica polyneuritiformis. 8
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. 8
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)]. 8
14058273 1963
47
Refsum's syndrome affecting a brother and two sisters. 8
13560885 1958
48
Heredopathia atactica polyneuritiformis. 8
13045168 1952
49
Heredopathia Atactica Polyneuritiformis (Refsum's Syndrome). 8
19993784 1951
50
Heredopathia atactica polyneuritiformis in children. 8
18140089 1949

Variations for Refsum Disease, Classic

ClinVar genetic disease variations for Refsum Disease, Classic:

6 (show top 50) (show all 82)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PHYH NM_006214.4(PHYH): c.164del (p.Leu55fs) deletion Pathogenic rs730882058 10:13337577-13337577 10:13295577-13295577
2 PHYH NM_006214.4(PHYH): c.805A> C (p.Asn269His) single nucleotide variant Pathogenic rs104894179 10:13325713-13325713 10:13283713-13283713
3 PHYH PHYH, 3-BP INS, 576GCC insertion Pathogenic
4 PHYH NM_006214.4(PHYH): c.526C> A (p.Gln176Lys) single nucleotide variant Pathogenic rs28939672 10:13330512-13330512 10:13288512-13288512
5 PHYH NM_006214.4(PHYH): c.610G> A (p.Gly204Ser) single nucleotide variant Pathogenic rs104894173 10:13330428-13330428 10:13288428-13288428
6 PHYH NM_006214.4(PHYH): c.824G> A (p.Arg275Gln) single nucleotide variant Pathogenic rs104894174 10:13325694-13325694 10:13283694-13283694
7 PEX7 NM_000288.4(PEX7): c.120C> G (p.Tyr40Ter) single nucleotide variant Pathogenic rs61753238 6:137143923-137143923 6:136822785-136822785
8 PEX7 NM_000288.4(PEX7): c.-45C> T single nucleotide variant Pathogenic rs267608252 6:137143759-137143759 6:136822621-136822621
9 PEX7 NM_000288.4(PEX7): c.875T> A (p.Leu292Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1805137 6:137219351-137219351 6:136898213-136898213
10 PHYH NM_006214.4(PHYH): c.823C> T (p.Arg275Trp) single nucleotide variant Pathogenic/Likely pathogenic rs104894178 10:13325695-13325695 10:13283695-13283695
11 PHYH NM_006214.4(PHYH): c.135-2A> G single nucleotide variant Pathogenic/Likely pathogenic rs201578674 10:13337608-13337608 10:13295608-13295608
12 PHYH NM_006214.4(PHYH): c.766_767del (p.Val256fs) deletion Likely pathogenic rs797045100 10:13325751-13325752 10:13283751-13283752
13 PHYH NM_006214.4(PHYH): c.414+2T> C single nucleotide variant Likely pathogenic rs1554784939 10:13336426-13336426 10:13294426-13294426
14 PHYH NM_006214.4(PHYH): c.1010_1012dup (p.Leu338_Ter339insHis) duplication Conflicting interpretations of pathogenicity rs566116760 10:13320306-13320308 10:13278306-13278308
15 PEX7 NM_000288.4(PEX7): c.340-10A> G single nucleotide variant Conflicting interpretations of pathogenicity rs267608255 6:137166743-137166743 6:136845605-136845605
16 PHYH NM_006214.4(PHYH): c.734G> A (p.Arg245Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs62619919 10:13325784-13325784 10:13283784-13283784
17 PEX7 NM_000288.4(PEX7): c.615C> T (p.Asp205=) single nucleotide variant Conflicting interpretations of pathogenicity rs147298444 6:137187853-137187853 6:136866715-136866715
18 PHYH NM_006214.4(PHYH): c.126A> G (p.Gln42=) single nucleotide variant Conflicting interpretations of pathogenicity rs150631501 10:13340195-13340195 10:13298195-13298195
19 PHYH NM_006214.4(PHYH): c.321G> A (p.Ser107=) single nucleotide variant Conflicting interpretations of pathogenicity rs115198308 10:13336521-13336521 10:13294521-13294521
20 PHYH NM_006214.4(PHYH): c.678+15C> T single nucleotide variant Conflicting interpretations of pathogenicity rs140995522 10:13330345-13330345 10:13288345-13288345
21 PHYH NM_006214.4(PHYH): c.643G> A (p.Gly215Ser) single nucleotide variant Uncertain significance rs7901902 10:13330395-13330395 10:13288395-13288395
22 PHYH NM_006214.4(PHYH): c.574G> A (p.Ala192Thr) single nucleotide variant Uncertain significance rs751660253 10:13330464-13330464 10:13288464-13288464
23 PHYH NM_006214.4(PHYH): c.245G> A (p.Arg82Gln) single nucleotide variant Uncertain significance rs886046830 10:13337496-13337496 10:13295496-13295496
24 PHYH NM_006214.4(PHYH): c.-20G> C single nucleotide variant Uncertain significance rs546291238 10:13342062-13342062 10:13300062-13300062
25 PHYH NM_006214.4(PHYH): c.*47G> A single nucleotide variant Uncertain significance rs180770135 10:13320254-13320254 10:13278254-13278254
26 PHYH NM_006214.4(PHYH): c.829-3C> A single nucleotide variant Uncertain significance rs116930123 10:13323113-13323113 10:13281113-13281113
27 PHYH NM_006214.4(PHYH): c.792C> T (p.His264=) single nucleotide variant Uncertain significance rs372047384 10:13325726-13325726 10:13283726-13283726
28 PHYH NM_006214.4(PHYH): c.679-11T> A single nucleotide variant Uncertain significance rs886046828 10:13325850-13325850 10:13283850-13283850
29 PHYH NM_006214.4(PHYH): c.581C> T (p.Thr194Met) single nucleotide variant Uncertain significance rs141554572 10:13330457-13330457 10:13288457-13288457
30 PEX7 NM_000288.4(PEX7): c.*305_*310del deletion Uncertain significance rs886061123 6:137234969-137234974 6:136913831-136913836
31 PEX7 NM_000288.4(PEX7): c.-35G> A single nucleotide variant Uncertain significance rs886061116 6:137143769-137143769 6:136822631-136822631
32 PEX7 NM_000288.4(PEX7): c.-3G> A single nucleotide variant Uncertain significance rs886061117 6:137143801-137143801 6:136822663-136822663
33 PEX7 NM_000288.3(PEX7): c.-88T> C single nucleotide variant Uncertain significance rs886061115 6:137143716-137143716 6:136822578-136822578
34 PEX7 NM_000288.4(PEX7): c.316G> C (p.Val106Leu) single nucleotide variant Uncertain significance rs886061121 6:137147584-137147584 6:136826446-136826446
35 PEX7 NM_000288.4(PEX7): c.748-10T> C single nucleotide variant Uncertain significance rs886061122 6:137193326-137193326 6:136872188-136872188
36 PEX7 NM_000288.4(PEX7): c.804-5C> T single nucleotide variant Uncertain significance rs369653173 6:137219275-137219275 6:136898137-136898137
37 PEX7 NM_000288.4(PEX7): c.961A> G (p.Ile321Val) single nucleotide variant Uncertain significance rs879706210 6:137234653-137234653 6:136913515-136913515
38 PEX7 NM_000288.4(PEX7): c.*38G> A single nucleotide variant Uncertain significance rs41288965 6:137234702-137234702 6:136913564-136913564
39 PEX7 NM_000288.4(PEX7): c.*272A> G single nucleotide variant Uncertain significance rs186705952 6:137234936-137234936 6:136913798-136913798
40 PEX7 NM_000288.4(PEX7): c.*305C> T single nucleotide variant Uncertain significance rs567568009 6:137234969-137234969 6:136913831-136913831
41 PHYH NM_006214.4(PHYH): c.606C> A (p.Asn202Lys) single nucleotide variant Uncertain significance rs201979258 10:13330432-13330432 10:13288432-13288432
42 PHYH NM_006214.4(PHYH): c.356C> T (p.Thr119Met) single nucleotide variant Uncertain significance rs34571629 10:13336486-13336486 10:13294486-13294486
43 PHYH NM_006214.4(PHYH): c.93A> C (p.Ser31=) single nucleotide variant Uncertain significance rs202198596 10:13340228-13340228 10:13298228-13298228
44 PHYH NM_006214.4(PHYH): c.76-9A> T single nucleotide variant Uncertain significance rs368542152 10:13340254-13340254 10:13298254-13298254
45 PHYH NM_006214.4(PHYH): c.*22T> G single nucleotide variant Uncertain significance rs186628076 10:13320279-13320279 10:13278279-13278279
46 PHYH NM_006214.4(PHYH): c.1009A> G (p.Asn337Asp) single nucleotide variant Uncertain significance rs758218321 10:13320309-13320309 10:13278309-13278309
47 PHYH NM_006214.4(PHYH): c.980G> A (p.Arg327Gln) single nucleotide variant Uncertain significance rs367851769 10:13320338-13320338 10:13278338-13278338
48 PHYH NM_006214.4(PHYH): c.601C> G (p.Arg201Gly) single nucleotide variant Uncertain significance rs143957922 10:13330437-13330437 10:13288437-13288437
49 PHYH NM_006214.4(PHYH): c.321G> T (p.Ser107=) single nucleotide variant Uncertain significance rs115198308 10:13336521-13336521 10:13294521-13294521
50 PEX7 NM_000288.4(PEX7): c.576C> T (p.Ile192=) single nucleotide variant Uncertain significance rs776411851 6:137187814-137187814 6:136866676-136866676

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

74 (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:

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 peroxisomal membrane GO:0005778 9.63 PEX7 PEX14 PEX1 HSD17B4 GNPAT CAT
2 peroxisomal matrix GO:0005782 9.61 SCP2 PHYH PEX7 HSD17B4 HACL1 GNPAT
3 peroxisome GO:0005777 9.36 SCP2 PHYH PEX7 PEX14 PEX1 HSD17B4
4 cytosol GO:0005829 10 SCP2 PHYH PEX7 PEX1 HSD17B4 HACL1

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.81 PEX7 PEX14 PEX1 AP1S1
2 fatty acid metabolic process GO:0006631 9.63 PHYH HSD17B4 HACL1 GNPAT CRAT AMACR
3 peroxisome organization GO:0007031 9.56 SCP2 PEX7 PEX14 PEX1
4 bile acid biosynthetic process GO:0006699 9.54 SCP2 HSD17B4 AMACR
5 protein import into peroxisome matrix GO:0016558 9.5 PEX7 PEX14 PEX1
6 fatty acid beta-oxidation GO:0006635 9.49 PEX7 HSD17B4
7 response to fatty acid GO:0070542 9.48 GNPAT CAT
8 alpha-linolenic acid metabolic process GO:0036109 9.46 SCP2 HSD17B4
9 fatty acid alpha-oxidation GO:0001561 9.43 PHYH HACL1
10 ether lipid biosynthetic process GO:0008611 9.4 PEX7 GNPAT
11 protein targeting to peroxisome GO:0006625 9.36 SCP2 PHYH PEX7 PEX14 PEX1 HSD17B4
12 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.26 SCP2 HSD17B4 CRAT AMACR

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

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring acyl groups GO:0016746 9.33 SCP2 GNPAT CRAT
2 cofactor binding GO:0048037 8.96 PHYH HACL1
3 signaling receptor binding GO:0005102 8.8 SCP2 PEX14 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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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44 MeSH
45 MESH via Orphanet
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49 NCI
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51 NDF-RT
54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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