Biotin Deficiency Can Cause Neurological Disorders

Multiple carboxylase deficiencies (both biotinidase and holocarboxylase synthetase types) that cause biotin deficiencies can lead to a number of neurological disorders, including:^{18, 21, 57}

• Ataxia
• Developmental delays
• Hypotonia
• Seizures
• Serious sensory and motor deficits

Spinal cord damage via progressive demyelination, although rare, can also occur with biotinidase deficiency . Symptoms can include:⁴⁹

• Blepharoconjunctivitis
• Fatigue
• Hair loss
• Lethargy
• Muscle weakness
• Optic nerve atrophy
• Respiratory problems (e.g., wheezing, difficulty breathing, rapid breathing)
• Visual impairment

In case studies, prompt biotin supplementation led to dramatic improvement of symptoms, suggesting that biotinidase deficiency should be considered as a possible cause of spinal cord demyelination with no other apparent diagnosis.⁴⁹

Most of these neurological problems associated with biotin deficiency are resolved with administration of biotin. However, the question of exactly how the lack of biotin impacts these central nervous system functions is still being investigated.⁴⁹

The Fatty Acid Connection

One line of inquiry has to do with biotin's role in the proper metabolism of essential fatty acids (EFAs). Insufficient biotin results in impaired synthesis of long-chain EFAs, even with adequate consumption of essential fatty acids. Abnormal metabolism or insufficient dietary intake of EFAs has been linked to the development or worsening of a number of diseases, including Alzheimer's disease.^{4, 8, 18}

PC Enzyme

Although biotin is essential for the synthesis of fatty acids that are crucial to brain health, experts suggest that this may not be the cause of brain dysfunction when biotin levels are low. Studies indicate that the neurological symptoms that appear with insufficient/deficient biotin levels are related to insufficient levels of the biotin-dependent pyruvate carboxylase enzyme (PC).¹⁸

Biotin in the Brain

Whether neurological disorders are due to inadequate EFA metabolism or PC biotinylation, animal and human studies corroborate that brain neurons need biotin to function properly. Evidence from animal studies suggests that biotin and biotinidase are highly expressed in the cerebellar motor and brainstem auditory nuclei, which corresponds to neurological symptoms when biotin is deficient. Although biotin was not found in central visual nuclei in this study, it has been reported found in retinal Muller cells - which may explain the visual loss and optic atrophy in biotin deficiency.⁵⁷

This suggests that these areas have greater need for biotin and are more susceptible to deficiencies. Further support for this came from autopsy examination of biotinidase-deficient human patients, which showed degeneration in these areas.⁵⁷

Crossing the Blood-Brain Barrier

Lack of availability of biotin to brain tissue can also be caused by transportation issues. Biotin is usually easily transported across the blood-brain barrier. However, studies show that a defect in biotin transport across the blood-brain barrier causes biotin-responsive basal ganglia disease , with sub-acute encephalopathy and multiple neurological symptoms, including:^{18, 58}

• Ataxia
• Confusion
• Developmental delays
• Dysarthria
• Dysphagia
• Hypotonia
• Seizures
• Supra nuclear facial nerve palsy

If left undiagnosed, the condition can progress to include spastic paraparesis, mental retardation, and dystonia. Conversely, administration of 5-10 mg/kg/day resolves symptoms, but they reappear within a month if treatment stops.⁵⁸