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Familial isolated deficiency of vitamin E(AVED)

MedGen UID:
341248
Concept ID:
C1848533
Disease or Syndrome
Synonyms: Ataxia with isolated vitamin E deficiency; Ataxia with vitamin E deficiency; AVED; Friedreich-like ataxia with selective vitamin E deficiency
SNOMED CT: Familial isolated vitamin E deficiency (702442008); Friedreich-like ataxia (702442008); Ataxia with vitamin E deficiency (702442008); Ataxia with isolated vitamin E deficiency (702442008); Friedreich ataxia phenotype with selective vitamin E deficiency (702442008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): TTPA (8q12.3)
 
Monarch Initiative: MONDO:0010188
OMIM®: 277460
Orphanet: ORPHA96

Definition

Ataxia with vitamin E deficiency (AVED) generally manifests in late childhood or early teens between ages five and 15 years. The first symptoms include progressive ataxia, clumsiness of the hands, loss of proprioception, and areflexia. Other features often observed are dysdiadochokinesia, dysarthria, positive Romberg sign, head titubation, decreased visual acuity, and positive Babinski sign. The phenotype and disease severity vary widely among families with different pathogenic variants; age of onset and disease course are more uniform within a given family, but symptoms and disease severity can vary even among sibs. [from GeneReviews]

Additional description

From MedlinePlus Genetics
Ataxia with vitamin E deficiency is a disorder that impairs the body's ability to use vitamin E obtained from the diet. Vitamin E is an antioxidant, which means that it protects cells in the body from the damaging effects of unstable molecules called free radicals. A shortage (deficiency) of vitamin E can lead to neurological problems, such as difficulty coordinating movements (ataxia) and speech (dysarthria), loss of reflexes in the legs (lower limb areflexia), and a loss of sensation in the extremities (peripheral neuropathy). Some people with this condition have developed an eye disorder called retinitis pigmentosa that causes vision loss. Most people who have ataxia with vitamin E deficiency start to experience problems with movement between the ages of 5 and 15 years. The movement problems tend to worsen with age.  https://medlineplus.gov/genetics/condition/ataxia-with-vitamin-e-deficiency

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
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- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Perseverative thought
MedGen UID:
66686
Concept ID:
C0233651
Mental or Behavioral Dysfunction
The repetitive production of the same response to different commands.
Clumsiness
MedGen UID:
66690
Concept ID:
C0233844
Sign or Symptom
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Dysdiadochokinesis
MedGen UID:
115975
Concept ID:
C0234979
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible.
Positive Romberg sign
MedGen UID:
66017
Concept ID:
C0240914
Finding
The patient stands with the feet placed together and balance and is asked to close his or her eyes. A loss of balance upon eye closure is a positive Romberg sign and is interpreted as indicating a deficit in proprioception.
Progressive cerebellar ataxia
MedGen UID:
140727
Concept ID:
C0393525
Disease or Syndrome
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Short term memory impairment
MedGen UID:
675230
Concept ID:
C0701811
Mental or Behavioral Dysfunction
A deficit in the retention of pieces of information (memory chunks) for a relatively short time (usually up to 30 seconds).
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Impaired proprioception
MedGen UID:
346424
Concept ID:
C1856691
Finding
A loss or impairment of the sensation of the relative position of parts of the body and joint position.
Delayed somatosensory central conduction time
MedGen UID:
867773
Concept ID:
C4022163
Finding
An abnormal increase (delay) in the somatosensory central conduction time (CCT), which can be measured from the peak of N13 to the peak of N20 (peak CCT) or from the onset of N11 to the onset of N20 (onset CCT).
Tendon xanthomatosis
MedGen UID:
450999
Concept ID:
C0221253
Disease or Syndrome
The presence of xanthomas (intra-and extra-cellular accumulations of cholesterol) extensor tendons (typically over knuckles, Achilles tendon, knee, and elbows).
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Increased LDL cholesterol concentration
MedGen UID:
154289
Concept ID:
C0549399
Finding
An elevated concentration of low-density lipoprotein cholesterol in the blood.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Decreased circulating vitamin E concentration
MedGen UID:
1853278
Concept ID:
C5779643
Finding
A reduced concentration of vitamin E in the blood circulation. Vitamin E is a lipophilic vitamin that is also known as alpha-tocopherol.
Xanthelasma
MedGen UID:
56357
Concept ID:
C0155210
Disease or Syndrome
The presence of xanthomata in the skin of the eyelid.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial isolated deficiency of vitamin E
Follow this link to review classifications for Familial isolated deficiency of vitamin E in Orphanet.

Professional guidelines

PubMed

Anheim M, Fleury M, Monga B, Laugel V, Chaigne D, Rodier G, Ginglinger E, Boulay C, Courtois S, Drouot N, Fritsch M, Delaunoy JP, Stoppa-Lyonnet D, Tranchant C, Koenig M
Neurogenetics 2010 Feb;11(1):1-12. Epub 2009 May 14 doi: 10.1007/s10048-009-0196-y. PMID: 19440741

Recent clinical studies

Therapy

Kohlschütter A, Finckh B, Nickel M, Bley A, Hübner C
Neurodegener Dis 2020;20(1):35-38. Epub 2020 Jul 3 doi: 10.1159/000508080. PMID: 32623435

Clinical prediction guides

Kohlschütter A, Finckh B, Nickel M, Bley A, Hübner C
Neurodegener Dis 2020;20(1):35-38. Epub 2020 Jul 3 doi: 10.1159/000508080. PMID: 32623435

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