Biotinidase deficiency: A novel vitamin recycling defect

  title={Biotinidase deficiency: A novel vitamin recycling defect},
  author={Barry Wolf and Robert E. Grier and Julie R Secor McVoy and Gregory S. Heard},
  journal={Journal of Inherited Metabolic Disease},
The recent finding that biotinidase deficiency is the primary biochemical defect in late-onset multiple carboxylase deficiency has stimulated new interest in the inherited disorders of biotin-dependent carboxylases. The clinical and biochemical features of biotinidase deficiency are discussed. We also speculate about two exciting areas currently being investigated: the localization of action of biotinidase, and the possible role of the enzyme as a binding or carrier protein for biotin. 

Biotinidase deficiency: Novel mutations and their biochemical and clinical correlates

Thirteen novel mutations in children with biotinidase deficiency are determined, including the first to be reported that alters the cysteine in the putative location crucial for ester formation and binding of the biotinyl‐moiety in the active site of the enzyme.

Enzyme studies in biotin-responsive disorders

There appear to be at least two underlying aetiologies for combined carboxylase deficiency; firstly, a failure of biotinylation of apocarboxylases due to a mutation of holocarboxylase synthetase (EC

Technical standards and guidelines for the diagnosis of biotinidase deficiency

These guidelines were developed to define and standardize laboratory procedures for enzymatic biotinidase testing, to delineate situations for which follow-up molecular testing is warranted, and to characterize variables that can influence test performance and interpretation of results.

The neurology of biotinidase deficiency.

  • B. Wolf
  • Medicine
    Molecular genetics and metabolism
  • 2011

Biotinidase deficiency: novel mutations in Algerian patients.

Impaired Biotinidase Activity Disrupts Holocarboxylase Synthetase Expression in Late Onset Multiple Carboxylase Deficiency*

It is proposed that biotinidase-deficient patients may develop a secondary HCS deficiency disrupting the altruistic tissue-specific biotin allocation mechanism that protects brain metabolism during biotin starvation.

Comparison of patients with complete and partial biotinidase deficiency: Biochemical studies

It is suggested that at least all patients with residual activities below 10% should be treated with biotin, because of discrete biochemical abnormalities found in a patient with residual biotinidase activity of 8.

Biotin and biotinidase deficiency

Biotin deficiency may be caused by insufficient dietary uptake of biotin, drug–vitamin interactions and, perhaps, by increased biotin catabolism during pregnancy and in smokers.

Development and characterization of a mouse with profound biotinidase deficiency: a biotin-responsive neurocutaneous disorder.




Biotinidase deficiency: the possible role of biotinidase in the processing of dietary protein-bound biotin.

The findings indicate that the primary enzyme defect in late-onset multiple carboxylase deficiency is in biotinidase activity and that the disorder is inherited as an autosomal recessive trait.

Two forms of biotin-responsive multiple carboxylase deficiency

  • L. Sweetman
  • Chemistry
    Journal of Inherited Metabolic Disease
  • 2005
It is proposed that holocarboxylase synthetase and intestinal biotin absorption are defective in the early and late forms respectively.

Impaired intestinal absorption of biotin in juvenile multiple carboxylase deficiency.

THE syndrome of biotin-responsive multiple carboxylase deficiency has two relatively distinct phenotypes: a neonatal form, with the onset of life-threatening lactic acidosis, seizures, and

Phenotypic variation in biotinidase deficiency.

Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency.

Results show that the primary defect in this patient is a mutation affecting holocarboxylase synthetase activity, and thus a genetic defect of the metabolism of biotin.

The biotin-dependent carboxylase deficiencies.

Clinical, biochemical, and genetic features of inherited metabolic disorders characterized by deficiencies of the four known human biotindependent enzymes are delineated and compared.

[Multiple biotin-dependent carboxylase deficiencies (author's transl)].

It is suggested that MCD could be of two types: impaired biotin metabolism (absorption, transport, activation) might result in generalization MCD involving ACC and defective holocarboxylase synthetase might lead to a pure mitochondrial MCD with fibroblastic deficiency and presumably skin integrity.

Biotin-responsive immunoregulatory dysfunction in multiple carboxylase deficiency

It is suggested that the PGE deficiency in MCD could result from an impaired activity of a biotin enzyme, acetyl CoA carboxylase, since the product of this enzyme reaction, malonyl CoA, is required for prostaglandin synthesis.


It is shown that biotinidase activity in rats is not enriched in intestinal brush border membranes but it is present in mucosa from all sections of the small intestine, and it is also in pancreatic homogenates, suggesting that biotinyl-peptides has an important role in increasing the bioavailability of dietary biotin.