Biotinidase Deficiency

Excerpt

Vitamins are vital components of every individual’s day-to-day chemical reactions and molecular processes. They are cofactors for reactions, antioxidants, hormones, and even vision. Vitamin deficiencies can be acquired by a lack of adequate environmental supplies or due to abnormal vitamin processing within intracellular pathways. Biotin is an essential vitamin obtained through the diet and efficiently recycled for further use. When this recycling mechanism does not work due to enzyme deficiency, patients experience significant morbidity and mortality. This condition, known as biotinidase deficiency, is inherited in an autosomal recessive fashion.

Biotin acts as a coenzyme for four carboxylation enzymes in the body: 3-methylcrotonyl-CoA carboxylase (MCC), pyruvate carboxylase (PC), acetyl-CoA carboxylase (ACC), and propionyl-CoA carboxylase (PCC). Biotinidase deficiency can be partial (10 to 30% of enzyme activity) or profound (less than 10% of enzyme activity), significantly impacting the treatment approach. Partial cases can have little or no symptoms. However, profound cases can lead to coma or death if treatment is not initiated rapidly. Biotinidase deficiency has varying clinical manifestations, affecting ophthalmologic, neurologic, dermatologic, and immunologic systems. Early recognition is critical as expeditious treatment could prevent or minimize clinical insult.

Treatment is very straightforward as patients need consistent and high doses of biotin administered. This simple treatment can reverse many symptoms of the disease if initiated promptly. Therefore, early diagnosis and treatment can prevent developmental delay and disability and improve quality of life. This is a key reason that this disorder is part of many newborn screenings.

The role of biotin in treating carboxylase deficiencies was first studied around 40 years ago. In 1971, patients with beta-methylcrotonylglycinuria, a carboxylase deficiency, clinically responded to biotin supplementation. Ten years later, Wolf et al. further observed a neonatal type of multiple carboxylase deficiency because of biotin deficiency.