Friday, March 29, 2024

Biotinidase Deficiency

Background

Biotinidase (BTD, [OMIM 609019]), a ubiquitous mammalian cell enzyme, is present in high levels in the serum, liver, and kidneys. Its primary enzymatic function is to cleave the vitamin biotin (also known as coenzyme R, vitamin H, or vitamin B7) from the organic compound, biocytin. Biotin is recycled in the body when biotinidase liberates biotin from endogenous and dietary proteins. Recycling maintains a pool of biotin to serve as a critical cofactor for gluconeogenesis, fatty acid synthesis, and branched chain amino acid catabolism. In biotinidase deficiency, biotin-dependent enzymes are affected, namely the 4 human carboxylases: acetyl-CoA carboxylase, propionyl-CoA carboxylase, β-methylcrotonyl-CoA carboxylase, and pyruvate CoA carboxylase. Biotinidase deficiency (OMIM 253260) diminishes or prevents biotin recycling and coenzyme activity required for stable metabolic function.

Multiple carboxylase deficiency (MCD) is one of many metabolic disorders that occur in the absence of the coenzyme activity of biotin. Known genetic causes of multiple carboxylase deficiency include holocarboxylase synthetase (HCS) deficiency and biotinidase deficiency. These enzyme deficiencies render the body unable to reuse and recycle the vitamin biotin.

Holocarboxylase synthetase deficiency is typically diagnosed in neonates. Older infants with multiple carboxylase deficiency usually have biotinidase deficiency. Both enzyme deficiencies are known to be treatment-responsive to biotin supplements.

The role of biotin to treat carboxylase deficiencies was first recognized over 40 years ago. In 1971, patients diagnosed with beta-methylcrotonylglycinuria, a carboxylase deficiency, were clinically responsive to supplemental biotin treatment.
Ten years later, Wolf and colleagues further characterized a neonatal form of multiple carboxylase deficiency due to biotin deficiency.

This inborn error of metabolism can result from either partial or complete absence of biotinidase. Biotinidase deficiency has a wide range of clinical manifestations, as it affects the human neurologic,
ophthalmologic, dermatologic, and immunologic systems. Despite its rarity, early recognition is imperative because expeditious treatment may prevent or minimize clinical insult.

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