Biotin deficiency

Physical • Rashes including red, patchy ones near openings (e.g. erythematous periorofacial macular rash) • Hair loss (alopecia) • Conjunctivitis • Paresthesias (pins and needles) and numbness • Fatigue, drowsiness and somnolence == Causes ==

• Total parenteral nutrition without biotin supplementation: Several cases of biotin deficiency in patients receiving prolonged total parenteral nutrition (TPN) therapy without added biotin have been reported. Therefore, all patients receiving TPN must also receive biotin at the recommended daily dose, especially if TPN therapy is expected to last more than 1 week. All hospital pharmacies currently include biotin in TPN preparations. • Anticonvulsant therapy: Prolonged use of certain drugs (especially highly common prescription anti-seizure medications such as phenytoin, primidone, and carbamazepine), may lead to biotin deficiency; however, valproic acid therapy is less likely to cause this condition. Some anticonvulsants (antiepileptic drugs) inhibit biotin transport across the intestinal mucosa. Evidence suggests that these anticonvulsants accelerate biotin catabolism, which means that it's necessary for people to take supplemental biotin, in addition to the usual minimum daily requirements, if they're treated with anticonvulsant medication(s) that have been linked to biotin deficiency. • Severe malnourishment • Prolonged oral antibiotic therapy: Prolonged use of oral antibiotics has been associated with biotin deficiency. Alterations in the intestinal flora caused by the prolonged administration of antibiotics are presumed to be the basis for biotin deficiency. • Genetic mutation: Mikati et al. (2006) reported a case of partial biotinidase deficiency (plasma biotinidase level of 1.3 nm/min/mL) in a 7-month-old boy. The boy presented with perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. The child's neurologic symptoms abated following biotin supplementation and antiepileptic drug therapy. DNA mutational analysis revealed that the child was homozygous for a novel E64K mutation and that his mother and father were heterozygous for the novel E64K mutation. Potential causes • Smoking: Recent studies • Excessive alcohol consumption (causes a significant reduction in plasma biotin levels) • Excessive consumption of antidiuretics or inadequate levels of antidiuretic hormone • Intestinal malabsorption caused by short bowel syndrome == Biochemistry ==

Biotin is a coenzyme for five carboxylases in the human body (propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and 2 forms of acetyl-CoA carboxylase.) Therefore, biotin is essential for amino acid catabolism, gluconeogenesis, and fatty acid metabolism. Biotin is also necessary for gene stability because it is covalently attached to histones. Biotinylated histones play a role in repression of transposable elements and some genes. Normally, the amount of biotin in the body is regulated by dietary intake, biotin transporters (monocarboxylate transporter 1 and sodium-dependent multivitamin transporter), peptidyl hydrolase biotinidase (BTD), and the protein ligase holocarboxylase synthetase. When any of these regulatory factors are inhibited, biotin deficiency could occur. == Diagnosis ==

The only reliable method for determining biotin deficiency is the abundance of biotinylated 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase in lymphocytes. The level of biotin in urine can be used to identify biotin-supplemented individuals, and the level of 3-hydroxyisovaleric acid in urine can (unreliably) detect biotin-deficient patients. == Treatment ==

In the United States, biotin supplements are readily available without a prescription in amounts ranging from 300 to 10,000 micrograms. 30 micrograms daily is identified as Adequate Intake for men and women 19 years and older. 35 micrograms daily is required for lactating women. Most healthy individuals meet these recommended intakes, however many still take up to 500 to 1,000 micrograms of biotin daily. == Epidemiology ==

Deficiency is rare Pregnancy, however, alters biomarkers of biotin and despite a regular biotin intake, approximately half of the pregnant women in the U.S. are marginally biotin deficient. == See also ==

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