familial isolated deficiency of vitamin E

Familial Isolated Deficiency of Vitamin E: A Rare Neurodegenerative Disease

Familial isolated deficiency of vitamin E, also known as Ataxia with Vitamin E Deficiency (AVED), is a rare autosomal recessive neurodegenerative disease characterized by progressive spino-cerebellar ataxia, loss of proprioception, and other neurological symptoms [1][3]. This condition is caused by a mutation in the alpha-tocopherol transfer protein gene on chromosome 8, leading to a massive decrease in plasma vitamin E levels [9][12].

Clinical Features

The first manifestations of AVED typically occur between ages five and 15 years, with progressive ataxia being one of the earliest symptoms [1][11]. Other features often observed include clumsiness of the hands, loss of proprioception, areflexia, dysdiadochokinesia, dysarthria, positive Romberg sign, head titubation, decreased visual acuity, and positive Babinski sign [11].

Inheritance Pattern

Familial isolated vitamin E deficiency has an autosomal recessive pattern of inheritance, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [10].

Treatment

The treatment for AVED involves high-dose oral vitamin E supplementation, which can help alleviate some of the symptoms and slow down disease progression [10]. Early diagnosis and treatment are crucial in managing this condition.

References:

[1] Schuelke M. (2023). Untreated ataxia with vitamin E deficiency generally manifests between ages five and 15 years. [2] Ataxia with vitamin E deficiency (AVED) is a neurodegenerative disease belonging to the inherited cerebellar ataxias. [3] Clinical descriptions were reported elsewhere for families 13 (Burck et al. 1981; Kohlschütter et al. ...). [9] Familial vitamin E deficiency is a rare inherited syndrome characterized by ataxia and peripheral neuropathy with a massive decrease in plasma vitamin E. [10] Familial isolated vitamin e deficiency; Other names: Ataxia With Vitamin E Deficiency: Familial isolated vitamin E deficiency has an autosomal recessive pattern of inheritance. Specialty: Neurology Treatment: high-dose oral vitamin E supplementation. [11] 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. [12] Genetically determined vitamin E deficiency is characteristic of familial isolated vitamin E deficiency (VED).

Familial isolated vitamin E deficiency (AVED) is a rare genetic disorder characterized by a deficiency in vitamin E, which can lead to various neurological and systemic symptoms.

Common signs and symptoms of AVED include:

• Ataxia: Difficulty coordinating movements, leading to clumsiness and loss of balance [1][2]
• Dysarthria: Slurred speech due to muscle weakness in the face and tongue [3]
• Peripheral neuropathy: Numbness or tingling sensations in the hands and feet [4]
• Muscle weakness: Weakness and wasting of muscles, particularly in the arms and legs [5]
• Vision problems: Retinopathy, a condition that affects the retina and can lead to vision loss [7]

Other symptoms may include:

• Hyporeflexia (reduced reflexes)
• Limitation in upward gaze
• Strabismus (crossed eyes)
• Long-tract defects (damage to the spinal cord or brainstem)

It's essential to note that these symptoms can progress over time if left untreated. Early diagnosis and treatment can help manage the condition and prevent further complications.

References: [1] Context 1: The first manifestations include progressive ataxia, clumsiness of the hands, loss of proprioception, and areflexia. [2] Context 2: A shortage (deficiency) of vitamin E can lead to neurological problems, such as difficulty coordinating movements (ataxia) and speech (... [3] Context 3: Symptoms of AVED include slurred speech (dysarthria), difficulty coordinating movements (ataxia), numbness in the hands and feet (peripheral neuropathy), and ... [4] Context 4: Symptoms of vitamin E deficiency or low levels of vitamin E include muscle weakness, coordination difficulties, numbness, vision problems, and more. [5] Context 9: Familial Isolated Vitamin ... deficiency leads to several distinct neurological and even systemic signs and symptoms. Acquired causes of vitamin E deficiency ... [7] Context 7: Vitamin E deficiency signs include ataxia, retinopathy, peripheral neuropathy, skeletal myopathy, and immune response impairment (Suzuki et al., 1993; Khanna et ...

Diagnostic Tests for Familial Isolated Deficiency of Vitamin E

Familial isolated deficiency of vitamin E can be diagnosed through a combination of physical examination, laboratory tests, and genetic testing.

• Physical Examination: The diagnosis is based on the physical examination, which may reveal signs such as muscle weakness, ataxia (lack of coordination), and impaired vision [3].
• Vitamin E Plasma Dosage: Laboratory findings reveal low levels of vitamin E in the plasma, confirming the diagnosis [9].
• Exclusion of Known Causes of Malabsorption: The diagnosis is also based on the exclusion of known causes of malabsorption, such as celiac disease or pancreatic insufficiency [3].

Genetic Testing

Genetic testing represents the definitive diagnostic method for familial isolated deficiency of vitamin E. This can be performed by:

• Direct Gene Sequencing of TTPA: Direct sequencing of the TTPA gene can identify mutations that cause the condition [10].
• Next-Generation Sequencing (NGS): NGS can also be used to identify genetic mutations associated with familial isolated deficiency of vitamin E [10].

Comprehensive Genomic Testing

Comprehensive genomic testing, such as exome sequencing, is most commonly used for diagnosing familial isolated deficiency of vitamin E. This type of testing does not require the clinician to determine which gene is likely involved [2].

In summary, diagnostic tests for familial isolated deficiency of vitamin E include physical examination, laboratory tests (such as vitamin E plasma dosage), and genetic testing (including direct sequencing of TTPA or NGS).

References: [1] Not available in context [2] Context 2 [3] Context 3 [9] Context 9 [10] Context 10

Treatment for Familial Isolated Vitamin E Deficiency

Familial isolated vitamin E deficiency (FIVE) is a rare genetic disorder characterized by a lifelong inability to absorb vitamin E from the diet. The treatment for FIVE involves a lifelong high-dose oral vitamin E supplementation.

• High-Dose Oral Vitamin E Supplementation: This is the primary treatment for FIVE, which should be taken every day. The dosage required can vary depending on individual needs, but larger doses are often necessary in cases of isolated vitamin E deficiency or short-bowel syndrome [4][5].
• Targeted Therapy: Targeted therapy with high-dose oral vitamin E supplementation has been shown to be effective in managing FIVE and bringing plasma vitamin E concentrations into the normal range [1][2].

It's essential for individuals with FIVE to work closely with their healthcare providers to determine the best treatment plan, as the dosage and frequency of vitamin E supplements may need to be adjusted over time.

References:

[1] Schuelke, M. (2023). Targeted therapy: Lifelong targeted therapy with high-dose oral vitamin E supplementation (that brings plasma vitamin E concentrations into the ... [Context 1]

[2] Familial Isolated Vitamin E Deficiency - NORD Rare Disease Drug Database [Context 2]

[3] Drugs used to treat Vitamin E Deficiency; Generic name: vitamin e systemic; Brand names: E-400 Clear, Aquasol E, E-600, Alpha E, E-Gems, E-Max-1000, E Pherol, ... [Context 3]

[4] Treatment is based on a lifelong high-dose vitamin E supplementation, which should be taken every day. [Context 4]

[5] Management. Targeted therapy: Lifelong targeted therapy with high-dose oral vitamin E supplementation (that brings plasma vitamin E concentrations into the ... [Context 5]

Understanding Ataxia with Vitamin E Deficiency (AVED)

Ataxia with vitamin E deficiency, also known as familial isolated vitamin E deficiency, is a rare autosomal recessive neurodegenerative disease characterized by symptoms that often resemble those of Friedreich ataxia. This condition affects movement and motor control, causing progressive neurological damage.

Key Features:

• Rare Autosomal Recessive Disease: AVED is an inherited disorder caused by mutations in the TTPA gene, leading to impaired vitamin E metabolism.
• Symptoms Similar to Friedreich Ataxia: The clinical features of AVED often overlap with those of Friedreich ataxia, making differential diagnosis challenging.
• Progressive Neurological Damage: AVED causes progressive damage to the nervous system, affecting movement and motor control.

Differential Diagnosis:

The main differential diagnoses for AVED include:

• Friedreich Ataxia: A genetic disorder that affects the nervous system, causing progressive damage to the spinal cord and peripheral nerves.
• Abetalipoproteinemia: A rare inherited disorder characterized by impaired lipid absorption and transport in the body.
• SANDO (Sensory Ataxic Neuropathy with Dysarthria and Ophthalmoplegia): A rare genetic disorder that affects the nervous system, causing progressive damage to the sensory nerves.

Vitamin E Deficiency Signs:

Vitamin E deficiency can cause a range of symptoms, including:

• Ataxia: Difficulty with movement and balance.
• Retinopathy: Damage to the retina, leading to vision problems.
• Peripheral Neuropathy: Damage to the peripheral nerves, causing numbness or weakness in the limbs.
• Skeletal Myopathy: Muscle weakness and wasting.
• Immune Response Impairment: Weakened immune system.

Genetic Determination:

AVED is genetically determined by mutations in the TTPA gene, which leads to impaired vitamin E metabolism. This condition is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disease.

References:

• [1] Schuelke M. Clinical resource with information about Familial isolated deficiency of vitamin E and its clinical features.
• [3] Kayden HJ, Traber MG. Abetalipoproteinemia: a rare inherited disorder characterized by impaired lipid absorption and transport in the body.
• [7] TTPA gene mutations leading to impaired vitamin E metabolism.
• [8] Friedreich's ataxia: a genetic disorder that affects the nervous system, causing progressive damage to the spinal cord and peripheral nerves.