Abetalipoproteinemia neuropathy

= = Abetalipoproteinemia Neuropathy == Abetalipoproteinemia neuropathy is a rare genetic disorder that affects the body's ability to properly absorb dietary fats, cholesterol, and fat-soluble vitamins. This condition is a subtype of abetalipoproteinemia, which is characterized by the absence of apolipoprotein B-containing lipoproteins in the blood. The neuropathy associated with this condition results from deficiencies in essential vitamins, particularly vitamin E, leading to neurological symptoms.

Etiology

Abetalipoproteinemia is caused by mutations in the MTTP gene, which encodes the microsomal triglyceride transfer protein. This protein is essential for the assembly and secretion of apolipoprotein B-containing lipoproteins. Without functional MTTP, the body cannot produce chylomicrons and very low-density lipoproteins (VLDL), leading to fat malabsorption and vitamin deficiencies.

Pathophysiology

The lack of apolipoprotein B-containing lipoproteins results in the malabsorption of fat and fat-soluble vitamins, particularly vitamin E. Vitamin E is crucial for protecting nerve cells from oxidative damage. Its deficiency leads to the degeneration of the nervous system, manifesting as neuropathy. The neuropathy in abetalipoproteinemia is primarily a sensory neuropathy, affecting the peripheral nerves.

Clinical Features

Patients with abetalipoproteinemia neuropathy typically present with:

• Progressive ataxia
• Loss of deep tendon reflexes
• Muscle weakness
• Loss of proprioception and vibratory sense
• Retinitis pigmentosa, leading to vision problems

Diagnosis

Diagnosis of abetalipoproteinemia neuropathy involves:

• Genetic testing for mutations in the MTTP gene
• Blood tests showing low levels of cholesterol and triglycerides
• Vitamin E deficiency
• Nerve conduction studies to assess the extent of neuropathy

Treatment

Management of abetalipoproteinemia neuropathy focuses on:

• High-dose vitamin E supplementation to prevent or slow the progression of neurological symptoms
• Dietary modifications to include medium-chain triglycerides, which do not require chylomicrons for absorption
• Regular monitoring of vitamin levels and neurological function

Prognosis

With early diagnosis and appropriate treatment, the progression of neurological symptoms can be slowed, and quality of life can be improved. However, untreated vitamin E deficiency can lead to irreversible neurological damage.

Research Directions

Ongoing research is focused on:

• Gene therapy approaches to correct the underlying genetic defect
• Novel therapies to enhance lipid absorption and vitamin delivery

NIH genetic and rare disease info

• NIH info on Abetalipoproteinemia neuropathy

Abetalipoproteinemia neuropathy is a rare disease.