| Refsum disease |
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Phytanic acid
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| Classification and external resources |
| Specialty |
neurology |
| ICD-10 |
G60.1 |
| ICD-9-CM |
356.3 |
| OMIM |
266500 |
| DiseasesDB |
11213 |
| eMedicine |
derm/705 |
| Patient UK |
Refsum disease |
| MeSH |
D012035 |
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[edit on Wikidata]
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Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid oxidase deficiency and phytanic acid storage disease,[1][2][3][4] is an autosomal recessive[5] neurological disease that results from the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991).[6][7] Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. Humans obtain the necessary phytanic acid primarily though diet. It is still unclear what function phytanic acid plays physiologically in humans, but has been found to regulate fatty acid metabolism in the liver of mice.[8]
Contents
- 1 Classification
- 2 Characteristics
- 3 Cause
- 4 Treatment
- 5 Biological sources of phytanic acid
- 6 See also
- 7 External links
- 8 References
Classification
Adult Refsum disease may be divided into the adult Refsum disease 1 and adult Refsum disease 2 subtypes. The former stems from mutations in the phytanoyl-CoA hydroxylase (PAHX aka PHYH) gene, on the PHYH locus at 10p13 on chromosome 6q22-24.[9] It was initially believed this was the sole mutation; however 55% of cases are now attributed to mutations in other genes.[10]
Refsum disease 2 stems from mutations in the peroxin 7 (PEX7) gene.[1][11] This mutation on the PEX7 gene is also on chromosome 6q22-24, and was found in patients presenting with accumulation of phytanic acid with no PHYH mutation.[9]
Adult Refsum disease should not be confused with infantile Refsum disease, a peroxisome biogenesis disorder resulting from deficiencies in the catabolism of very long chain fatty acids and branched chain fatty acids (such as phytanic acid) and plasmalogen biosynthesis.[1][11]
Characteristics
Individuals with Refsum disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation or remission occur. Symptoms also include ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including retinitis pigmentosa, cataracts, and night blindness.[12] In 80% of patients diagnosed with Refsum disease, sensorineural hearing loss has been reported.[8] This is hearing loss as the result of damage to the inner ear or the nerve connected to ear to the brain.
Cause
Refsum disease is a peroxisomal disorder caused by the impaired alpha-oxidation of branched chain fatty acids resulting in buildup of phytanic acid and its derivatives in the plasma and tissues. This may be due to deficiencies of phytanoyl-CoA hydroxylase or peroxin-7 activity. In general, Refsum disease is caused by PHYH mutations.[1][11]
PEX7 gene mutations can interrupt the peroxisomal transport of proteins as this gene codes for the peroxin 7 protein receptor. These mutations in the PEX7 gene generally lead to rhizomelic chondrodysplasia punctata type 1- which impairs development of many parts of the body.[9] Refsum disease is inherited in an autosomal recessive pattern, meaning that it requires both copies of the mutation to inherit the disease.[citation needed]
Treatment
Since phytanic acid is not produced in the human body, individuals with Refsum disease are commonly placed on a phytanic acid-restricted diet and avoid the consumption of fats from ruminant animals and certain fish, such as tuna, cod, and haddock.[12][13] Grass feeding animals and their milk are also avoided.[10] Recent research has shown that CYP4 isoform enzymes could help reduce the over-accumulation of phytanic acid in vivo.[14] Plasmapheresis is another medical intervention used to treat patients. This involves the filtering of blood to ensure there is no accumulation of phytanic acid.[10]
Biological sources of phytanic acid
In ruminant animals, the gut fermentation of consumed plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fats.[15] Although humans cannot derive significant amounts of phytanic acid from the consumption of chlorophyll present in plant materials, it has been proposed that the great apes (bonobos, chimpanzees, gorillas, and orangutans) can derive significant amounts of phytanic acid from the hindgut fermentation of plant materials.[16]
See also
- The Myelin Project
- List of cutaneous conditions
External links
- GeneReview/NCBI/NIH/UW entry on Refsum Disease
References
- ^ a b c d Online 'Mendelian Inheritance in Man' (OMIM) 266500
- ^ Freedberg; et al. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. p. 499. ISBN 0-07-138076-0.
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 564. ISBN 0-7216-2921-0.
- ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
- ^ Jayaram, H.; Downes, S. M. (March 2008). "Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report". Journal of Medical Case Reports (Free full text) 2: 80. doi:10.1186/1752-1947-2-80. PMC 2275283. PMID 18336720.
- ^ Refsum S (1945). "Heredoataxia hemeralopica polyneuritiformis - et tidligere ikke beskrevet familiært syndrom? En foreløbig meddelelse". Nordisk Medicin (in Norwegian) 28: 2682–6.
- ^ Refsum S (1946). "Heredopathia atactica polyneuritiformis. A familial syndrome not hitherto described. A contribution to the clinical study of hereditary diseases of the nervous system". Acta psych. neur. (Suppl.38): 1–303.
- ^ a b Nogueira, C.; Meehan, T. & O’Donoghue, G. (2014). "Refsum's Disease and Cochlear Implantation". Annals Of Otology, Rhinology & Laryngology 123 (6): 425–427.
- ^ a b c Lambert-Hamill, M.; Mitchell, J.; Wierzbicki, A. S.; Haasjes, J.; Brites, P.; Waterham, H. R.; et al. (2003). "Identification of PEX7 as the Second gene involved in Refsum disease". The American Journal of Human Genetics 72 (2): 471–477.
- ^ a b c Metoyer, K. "Adult Refsum Disease. In C. Noggle". The encyclopedia of neuropsychological disorders.
- ^ a b c Online 'Mendelian Inheritance in Man' (OMIM) 266510
- ^ a b National Institutes of Health. "Synonym(s): Phytanic Acid Storage Disease, Heredopathia Atactica Polyneuritiformis <Internet>". Retrieved 8 July 2007.
- ^ Baldwin, R. J.; et al. (2010). "The effectiveness of long-term dietary therapy in the treatment of adult Refsum disease". J Neurol Neurosurg Psychiatry 81 (9): 954–957. doi:10.1136/jnnp.2008.161059. PMID 20547622.
- ^ Xu F, Ng VY, Kroetz DL, de Montellano PR (2006). "CYP4 isoform specificity in the omega-hydroxylation of phytanic acid, a potential route to elimination of the causative agent of Refsum's disease". J. Pharmacol. Exp. Ther. 318 (2): 835–9. doi:10.1124/jpet.106.104976. PMID 16707724.
- ^ Verhoeven, N. M.; Wanders, R. J.; Poll-The, B. T.; Saudubray, J. M.; Jakobs, C. (1998). "The metabolism of phytanic acid and pristanic acid in man: a review". Journal of Inherited Metabolic Disease 21 (7): 697–728. doi:10.1023/A:1005476631419. PMID 9819701.
- ^ Watkins, P. A.; Moser, A. B.; Toomer, C. B.; Steinberg, S. J.; Moser, H. W.; Karaman, M. W.; Ramaswamy, K.; Siegmund, K. D.; Lee, D. R.; Ely, J. J.; Ryder, O. A.; Hacia, J. G. (2010). "Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions". BMC Physiology 10: 19. doi:10.1186/1472-6793-10-19. PMC 2964658. PMID 20932325.
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Nervous system pathology, PNS, somatic (G50–G64, 350–357)
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Nerve, nerve root, plexus
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Cranial nerve
disease |
- V Trigeminal neuralgia
- Anesthesia dolorosa
- VII Facial nerve paralysis
- Bell's palsy
- Melkersson–Rosenthal syndrome
- Parry–Romberg syndrome
- Central seven
- XI Accessory nerve disorder
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Radiculopathy,
plexopathy |
- brachial plexus Brachial plexus lesion
- Thoracic outlet syndrome
- Phantom limb
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Mono-
neuropathy |
| Upper limb |
| median nerve: |
- Carpal tunnel syndrome
- Ape hand deformity
|
|
| ulnar nerve: |
- Ulnar nerve entrapment
- Froment's sign
- Guyon's canal syndrome
- Ulnar claw
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| radial nerve: |
- Radial neuropathy
- Wrist drop
- Cheiralgia paresthetica
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| long thoracic nerve: |
- Winged scapula
- Backpack palsy
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| Lower limb |
| lateral cutaneous nerve of thigh: |
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| tibial nerve: |
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| plantar nerve: |
|
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| superior gluteal nerve: |
|
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| sciatic nerve: |
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| General |
- Causalgia
- Mononeuritis multiplex
- Neuropathy Neuralgia/Neuritis
- Nerve compression syndrome
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Polyneuropathies/Polyradiculoneuropathy
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| HMSN |
- Charcot–Marie–Tooth disease
- Dejerine–Sottas disease
- Refsum's disease
- Hereditary spastic paraplegia
- Hereditary neuropathy with liability to pressure palsy
- Familial amyloid neuropathy
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| Autoimmune/demyelinating |
- Guillain–Barré syndrome
- Chronic inflammatory demyelinating polyneuropathy
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| Other |
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Genetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders (E80.3, 277.86)
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| Peroxisome biogenesis disorder |
- Zellweger syndrome
- Neonatal adrenoleukodystrophy
- Infantile Refsum disease
- Adult Refsum disease-2
- RCP 1
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| Enzyme-related |
- Acatalasia
- RCP 2&3
- Mevalonate kinase deficiency
- D-bifunctional protein deficiency
- Adult Refsum disease-1
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| Transporter-related |
- X-linked adrenoleukodystrophy
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| Lysosomal |
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See also: proteins, intermediates
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