Biotinidase Deficiency

Excerpt

Vitamins are vital components of daily biochemical reactions and molecular processes. These substances function as cofactors, antioxidants, hormones, and mediators of vision. Vitamin deficiencies can result from inadequate dietary intake or abnormal intracellular processing. Biotin is an essential vitamin obtained from the diet and efficiently recycled for continued use. Failure of this recycling mechanism due to enzyme deficiency causes significant morbidity and mortality. Biotinidase deficiency, an autosomal recessive condition, is the most common cause.

Biotin serves as a coenzyme for 4 carboxylation enzymes: 3-methylcrotonyl-CoA carboxylase (MCC), pyruvate carboxylase, acetyl-CoA carboxylase (ACC), and propionyl-CoA carboxylase (PCC). Biotinidase deficiency is classified as profound (0%-10% enzyme activity) or partial (10%-30% enzyme activity), with classification guiding the treatment approach. Clinical manifestations vary and may involve ophthalmologic, neurologic, dermatologic, and immunologic systems. Partial cases are often asymptomatic or have mild symptoms, whereas profound cases may progress to seizures, developmental delay, vision or hearing loss, metabolic acidosis, and, without treatment, coma or death. Early recognition is critical, as prompt biotin supplementation can prevent or minimize irreversible complications.

Management is straightforward because patients require consistent, high doses of biotin. This intervention can reverse or halt the progression of many symptoms when initiated promptly. Early diagnosis and treatment can prevent developmental delay, reduce long-term disability, and improve quality of life.

Biotinidase deficiency is included in many newborn screening programs worldwide and in all 50 states in the U.S. The therapeutic role of biotin in carboxylase deficiencies was first investigated approximately 40 years ago. In 1971, patients with β-methylcrotonylglycinuria, a carboxylase deficiency, demonstrated clinical response to biotin supplementation. A decade later, Wolf et al identified a neonatal form of multiple carboxylase deficiency caused by biotin deficiency.