Display Settings:

Format

Send to:

Choose Destination

Phytanic acid storage disease(RDPA)

MedGen UID:
11161
Concept ID:
C0034960
Disease or Syndrome
Synonyms: adult Refsum disease; Disorder of cornification 11 (phytanic acid type); Doc 11 (phytanic acid type); Herditary sensory and motor neuropathy type 4; hereditary motor and sensory neuropathy Type IV; Heredopathia atactica polyneuritiformis; HMSN 4; HMSN IV; HMSN type IV; Hypertrophic neuropathy of Refsum; PEX7-Related Refsum Disease; PHYH-Related Refsum Disease; Phytanic acid oxidase deficiency; RDPA; Refsum Disease; Refsum disease with increased pipecolic acidemia; REFSUM DISEASE, ADULT, 1; REFSUM DISEASE, CLASSIC; Refsum syndrome; Refsum's disease; Rhizomelic Chondrodysplasia Punctata Type 1
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Hereditary motor and sensory neuropathy type IV (25362006); Heredoataxic atactica polyneuritiformis (25362006); Heredoataxic hemeralopica polyneuritiformis (25362006); Hereditary motor and sensory neuropathy, type IV (25362006); HSMN IV (25362006); HSMN IV (25362006); Phytanic acid storage disease (25362006); Phytanic acid storage disease (25362006); Refsum's disease (25362006); Heredopathia atactica polyneuritiformis (25362006); Refsum syndrome (25362006); Heredoataxia hemeralopica polyneuritiformis (25362006); Refsum-Thiébaut disease (25362006); Hereditary sensory-motor neuropathy, type IV (25362006); Refsum-Thiebaut disease (25362006); HMSN IV (25362006)
 
Genes: PHYH; PEX7
Cytogenetic locations: 10p13; 6q23.3
OMIM®: 266500
Orphanet: ORPHA773

Disease characteristics

Excerpted from the GeneReview: Refsum Disease
Refsum disease is characterized by anosmia (a universal finding) and early-onset retinitis pigmentosa with variable combinations of neuropathy, deafness, ataxia, and ichthyosis. Onset of symptoms ranges from age seven months to over age 50 years. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems which develop later in life.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Ronald JA Wanders  |  Hans R Waterham  |  Bart P Leroy   view full author information

Additional descriptions

From OMIM
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.  http://www.omim.org/entry/266500
From GHR
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.  http://ghr.nlm.nih.gov/condition/refsum-disease

Clinical features

Abnormal renal physiology
MedGen UID:
489768
Concept ID:
CN168062
Finding
An abnormal functionality of the kidney.
Anosmia
MedGen UID:
504449
Concept ID:
CN000428
Finding
An inability to perceive odors. This is a general term describing inability to smell arising in any part of the process of smelling from absorption of odorants into the nasal mucous overlying the olfactory epithelium, diffusion to the cilia, binding to olfactory receptor sites, generation of action potentials in olfactory neurons, and perception of a smell.
Miosis
MedGen UID:
6409
Concept ID:
C0026205
Finding
Pupillary constriction. This may result from congenital absence of the dilatator pupillary muscle, defective sympathetic innervation, or irritation of the CONJUNCTIVA or CORNEA.
Cataract
MedGen UID:
368085
Concept ID:
C1962983
Finding
Nystagmus
MedGen UID:
409575
Concept ID:
C1963184
Finding
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Retinitis pigmentosa
MedGen UID:
504473
Concept ID:
CN000477
Finding
Hereditary degeneration and atrophy of the retina.
Retinal degeneration
MedGen UID:
504488
Concept ID:
CN000512
Finding
A deterioration of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality.
Night blindness
MedGen UID:
504543
Concept ID:
CN000623
Finding
Inability to see well at night or in poor light.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Hyporeflexia
MedGen UID:
101804
Concept ID:
C0151888
Finding
Increased CSF protein
MedGen UID:
329971
Concept ID:
C1806780
Finding
Anosmia
MedGen UID:
504449
Concept ID:
CN000428
Finding
An inability to perceive odors. This is a general term describing inability to smell arising in any part of the process of smelling from absorption of odorants into the nasal mucous overlying the olfactory epithelium, diffusion to the cilia, binding to olfactory receptor sites, generation of action potentials in olfactory neurons, and perception of a smell.
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Sensory impairment
MedGen UID:
505546
Concept ID:
CN003134
Finding
An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hyesthesia) refers to a reduction in cutaneous sensation to a specific type of testing.
Sensorimotor neuropathy
MedGen UID:
429082
Concept ID:
CN006238
Finding
Short fourth metatarsal
MedGen UID:
336358
Concept ID:
C1848514
Finding
Multiple epiphyseal dysplasia
MedGen UID:
505318
Concept ID:
CN002413
Finding
Ichthyosis
MedGen UID:
429191
Concept ID:
CN007091
Finding
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Cardiac arrhythmia
MedGen UID:
2039
Concept ID:
C0003811
Pathologic Function
An arrhythmia is a problem with the rate or rhythm of your heartbeat. It means that your heart beats too quickly, too slowly, or with an irregular pattern. When the heart beats faster than normal, it is called tachycardia. When the heart beats too slowly, it is called bradycardia. The most common type of arrhythmia is atrial fibrillation, which causes an irregular and fast heart beat. Many factors can affect your heart's rhythm, such as having had a heart attack, smoking, congenital heart defects, and stress. Some substances or medicines may also cause arrhythmias. . Symptoms of arrhythmias include: -Fast or slow heart beat. -Skipping beats. -Lightheadedness or dizziness. -Chest pain. -Shortness of breath . -Sweating . Your doctor can run tests to find out if you have an arrhythmia. Treatment to restore a normal heart rhythm may include medicines, an implantable cardioverter-defibrillator (ICD) or pacemaker, or sometimes surgery. . NIH: National Heart, Lung, and Blood Institute.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
hypertrophy or enlargement of the heart.
Congestive heart failure
MedGen UID:
504881
Concept ID:
CN001488
Finding
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Cardiomyopathy
MedGen UID:
504883
Concept ID:
CN001491
Finding
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Elevated levels of phytanic acid
MedGen UID:
429588
Concept ID:
CN009400
Finding
An abnormal elevation of phytanic acid.
Limb muscle weakness
MedGen UID:
500963
Concept ID:
CN003336
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Short fourth metatarsal
MedGen UID:
336358
Concept ID:
C1848514
Finding
Pes cavus
MedGen UID:
425071
Concept ID:
CN001601
Finding
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
Limb muscle weakness
MedGen UID:
500963
Concept ID:
CN003336
Finding
Reduced strength and weakness of the muscles of the arms and legs.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGPhytanic acid storage disease

Recent clinical studies

Etiology

Lindström K, Breimer ME, Jovall PA, Lanne B, Pimlott W, Samuelsson BE
J Biochem 1992 Mar;111(3):337-45. PMID: 1587795
Wanders RJ, Boltshauser E, Steinmann B, Spycher MA, Schutgens RB, van den Bosch H, Tager JM
J Neurol Sci 1990 Aug;98(1):1-11. PMID: 1700075

Diagnosis

Weinstein R
J Clin Apher 1999;14(4):181-4. PMID: 10611628
Yamamoto S, Onozu H, Yamada N, Hayasaka S, Watanabe A
Ophthalmologica 1995;209(5):251-5. PMID: 8570147
Budden SS, Kennaway NG, Buist NR, Poulos A, Weleber RG
J Pediatr 1986 Jan;108(1):33-9. PMID: 2418187
Weleber RG, Tongue AC, Kennaway NG, Budden SS, Buist NR
Arch Ophthalmol 1984 Sep;102(9):1317-21. PMID: 6206835
Scotto JM, Hadchouel M, Odievre M, Laudat MH, Saudubray JM, Dulac O, Beucler I, Beaune P
J Inherit Metab Dis 1982;5(2):83-90. PMID: 6188882

Therapy

Weinstein R
J Clin Apher 1999;14(4):181-4. PMID: 10611628
Robertson EF, Poulos A, Sharp P, Manson J, Wise G, Jaunzems A, Carter R
Eur J Pediatr 1988 Feb;147(2):133-42. PMID: 2452736
Djupesland G, Flottorp G, Refsum S
Neurology 1983 Feb;33(2):237-40. PMID: 6185882

Clinical prediction guides

Scotto JM, Hadchouel M, Odievre M, Laudat MH, Saudubray JM, Dulac O, Beucler I, Beaune P
J Inherit Metab Dis 1982;5(2):83-90. PMID: 6188882

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...