Biotinidase Deficiency and Carboxylase Disorders

Biotinidase deficiency is an autosomal recessive metabolic disorder in which reduced activity of the biotin‐recycling enzyme leads to insufficient availability of free biotin, a vital cofactor for four essential carboxylase enzymes. These carboxylases participate in fatty acid synthesis, gluconeogenesis and branched‐chain amino acid catabolism. Untreated, affected individuals develop dermatological lesions, neurological dysfunction, metabolic acidosis and, in severe cases, permanent neurological sequelae. Carboxylase disorders also include holocarboxylase synthetase deficiency, in which impaired attachment of biotin to apocarboxylases causes multiple carboxylase deficiency. Infants present with lactic acidosis, hypotonia, seizures and skin manifestations but typically show rapid clinical improvement following pharmacological biotin supplementation. Advances in molecular genetics have elucidated over a hundred pathogenic variants in the BTD and HLCS genes, refined genotype–phenotype correlations and informed newborn‐screening programmes worldwide. Early detection through newborn or carrier screening and prompt biotin therapy have transformed outcomes, preventing irreversible damage and underscoring the global importance of these treatable disorders.

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Biotinidase Deficiency and Carboxylase Disorders publication trend

The graph below shows the total number of articles in biotinidase deficiency and carboxylase disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Biotinidase: Enzyme responsible for releasing free biotin from dietary and endogenous sources to support carboxylase function.

Carboxylase: Enzyme that catalyses carboxylation reactions, requiring biotin as a cofactor, essential in gluconeogenesis and lipid metabolism.

Holocarboxylase synthetase: Enzyme that covalently attaches biotin to apocarboxylases; its deficiency leads to multiple carboxylase deficiency.

Newborn screening: Public‐health programme for early detection of congenital disorders through biochemical assays in dried blood spots.

Reproductive carrier screening: Genetic testing of asymptomatic individuals to identify heterozygous carriers of pathogenic variants before conception.

References

1. Evaluating reproductive carrier screening using biotinidase deficiency as a model: Variants identified, variant rates, and management. Genetics in Medicine (2024).
2. Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives. International Journal of Molecular Sciences (2024).
3. Clinical, biochemical, and genetic analysis of 28 Chinese patients with holocarboxylase synthetase deficiency. Orphanet Journal of Rare Diseases (2023).