Rare Neurology News

Disease Profile

Ataxia with vitamin E deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

All ages

ageofonset-all.svg

ICD-10

G11.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

AVED; Ataxia with isolated vitamin E deficiency; Familial isolated deficiency of vitamin E;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

Ataxia with vitamin E deficiency (AVED) is a progressive disease affecting motor control and movement. Symptoms of AVED include slurred speech (dysarthria), difficulty coordinating movements (ataxia), numbness in the hands and feet (peripheral neuropathy), and progressive leg weakness. Some affected individuals may experience vision loss due to damage to the back of the eye (retinitis pigmentosa). Symptoms typically begin during childhood or adolescence and worsen with age, resulting in the need for a wheelchair by early adulthood. AVED is caused by a mutation to the TTPA gene. When this gene is damaged, vitamin E cannot be distributed throughout the body. Vitamin E is important because it protects the cells of the neurological system (neurons) from dangerous molecules called free radicals. AVED is inherited in an autosomal recessive manner. Treatment for AVED includes vitamin E supplements, which will prevent AVED from developing if given before symptoms begin and may reverse some neurological symptoms if begun after AVED develops.[1][2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal pyramidal sign
0007256
Areflexia
Absent tendon reflexes
0001284
Muscle weakness
Muscular weakness
0001324
30%-79% of people have these symptoms
Dysarthria
Difficulty articulating speech
0001260
Dysdiadochokinesis
Difficulty performing quick and alternating movements
0002075
Dysmetria
Lack of coordination of movement
0001310
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Nyctalopia
Night blindness
Night-blindness
Poor night vision

[ more ]

0000662
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Pes cavus
High-arched foot
0001761
Scoliosis
0002650
Sensory neuropathy
Damage to nerves that sense feeling
0000763
5%-29% of people have these symptoms
Abnormality of retinal pigmentation
0007703
Abnormality of visual evoked potentials
0000649
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Diabetes mellitus
0000819
Dystonia
0001332
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hypertonia
0001276
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Tremor
0001337
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
Percent of people who have these symptoms is not available through HPO
Ataxia
0001251
Autosomal recessive inheritance
0000007
Hypercholesterolemia
Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol

[ more ]

0003124
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Increased LDL cholesterol concentration
Increased circulating LDL level
Increased LDL cholesterol

[ more ]

0003141
Low levels of vitamin E
Vitamin E deficiency
0100513
Tendon xanthomatosis
0010874
Xanthelasma
Fatty deposits in skin around the eyes
Fatty deposits on eyelids

[ more ]

0001114

Diagnosis

AVED may be suspected in individuals who have the following findings at the beginning of puberty:[2]

  • Progressive ataxia
  • Clumsiness of the hands
  • Loss of the ability to know where one's body is in space (proprioception)
  • Absent reflexes (areflexia)
  • The inability to perform rapid, alternating movements (dysdiadochokinesia)
  • A tendency to sway or fall while standing upright with the feet together, arms stretched out and the eyes closed (positive Romberg sign)
  • A nodding movement of the head (titubation)
  • Decreased visual sharpness (acuity)
  • Positive Babinski sign (upward movement of the big toe and fanning of the feet after the sole of the foot has been firmly stroked)
  • Macular atrophy (wasting away of the cells that form the part of our eye responsible for central vision)
  • Retinitis pigmentosa (eye disease in which there is damage to the retina)

Laboratory studies typically show a reduced plasma vitamin E concentration but normal levels of lipoproteins (proteins that combine with and transport fat or other lipids in the blood). Other studies that may be useful include: nerve conduction studies, brain imaging, and studies of nerve tissues.[2][3]

Although no universal diagnostic guidelines are available, researchers suggest that diseases that cause fat malabsorption, such as abetalipoproteinemia should be ruled out. Genetic testing finding two TTPA gene mutations may be useful to confirm the diagnosis.[2][3]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for AVED requires lifelong high dose supplementation of vitamin E. When treated early, some symptoms, such as ataxia and intellectual decline, can be reversed. In older patients, treatment may slow disease progression, but some symptoms remain.[2][3]

    Research indicates that if vitamin E treatment is initiated in presymptomatic individuals with two mutations in the TTPA gene (e.g., younger sibs of an affected individual), the symptoms of AVED will not develop.[2]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Ataxia with vitamin E deficiency. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Ataxia with vitamin E deficiency. Click on the link to view a sample search on this topic.

          References

          1. Ataxia with vitamin E deficiency. Genetics Home Reference; July 5 2016; https://ghr.nlm.nih.gov/condition/ataxia-with-vitamin-e-deficiency.
          2. Markus Schuelke. Ataxia with Vitamin E deficiency. GeneReveiws. October 13, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1241/. Accessed 11/17/2016.
          3. Mathieu ANHEIM. Ataxia with vitamin E deficiency. Orphanet. February 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=96. Accessed 11/17/2016.

          Rare Neurology News