How does abetalipoproteinemia (a genetic disorder characterized by the inability to fully assemble and secrete lipoproteins) lead to ataxia (a lack of muscle coordination which can affect speech, eye movements, and ability to swallow, walk and perform other physical tasks)?

From the Guidelines

Abetalipoproteinemia leads to ataxia primarily due to vitamin E deficiency, which is a result of the inability to fully assemble and secrete lipoproteins, essential for the absorption of fat-soluble vitamins 1.

Pathophysiology

• The condition is characterized by the absence of serum apoB-containing lipoproteins, leading to undetectable LDL-C and deficiency of lipid-soluble vitamins, including vitamin E 1.
• The demyelination that leads to neurological presentations, such as ataxia, seems to be associated with vitamin E deficiency, rather than the absence of LDL-C 1.
• Vitamin E supplementation has been shown to halt further neurological degeneration and improve symptoms 1.

Clinical Implications

• Affected individuals with abetalipoproteinemia often present with severe neurological manifestations, including ataxia, due to the deficiency of lipid-soluble vitamins 1.
• Lifelong supplementation with high-dose vitamin E is essential to prevent further neurological degeneration and improve symptoms 1.
• In cases of fat malabsorption, vitamin E supplementation (200 mg/day) can improve neurological symptoms after a few months, following normalization of vitamin E status 1.

From the Research

Abetalipoproteinemia and Ataxia

• Abetalipoproteinemia is a genetic disorder that leads to the inability to fully assemble and secrete lipoproteins, resulting in fat malabsorption and deficiency of fat-soluble vitamins, including vitamin E 2, 3, 4, 5, 6.
• The deficiency of vitamin E in abetalipoproteinemia can cause ataxia, a lack of muscle coordination that can affect speech, eye movements, and ability to swallow, walk, and perform other physical tasks 2, 3, 4, 5, 6.
• Ataxia in abetalipoproteinemia is often characterized as spinocerebellar ataxia, which can be prevented or delayed with early vitamin E therapy 4.
• The neuropathological changes in patients with abetalipoproteinemia and vitamin E deficiency resemble those seen in vitamin E-deficient monkeys, and include progressive ataxia, hyporeflexia, and proprioceptive loss 4.

Mechanism of Ataxia in Abetalipoproteinemia

• The exact mechanism of ataxia in abetalipoproteinemia is not fully understood, but it is thought to be related to the deficiency of vitamin E and other fat-soluble vitamins 2, 3, 4, 5, 6.
• Vitamin E plays a crucial role in maintaining normal neurological function, and its deficiency can lead to neurological disorders, including ataxia 3, 4.
• The deficiency of vitamin E in abetalipoproteinemia can also lead to peripheral neuropathy, which can contribute to the development of ataxia 2, 3, 4, 5, 6.

Clinical Features of Abetalipoproteinemia

• Abetalipoproteinemia is a rare autosomal recessive disorder that typically manifests in infancy with steatorrhea, vomiting, and failure to thrive 6.
• The disease can progress to include a variety of symptoms, including hematological, neuromuscular, and ophthalmological symptoms, if left untreated 6.
• Early recognition and treatment of abetalipoproteinemia can prevent or delay the development of complications, including ataxia, and improve the prognosis 2, 6.