Biotin is a water-soluble vitamin, generally classified as a B-complex vitamin. After the initial discovery of biotin, nearly forty years of research were required to establish it as a vitamin. Biotin is required by all organisms but can only be synthesized by bacteria, yeasts, molds, algae, and some plant species.

Function

In its physiologically active form biotin is attached at the active site of four important enzymes, known as carboxylases. Each carboxylase catalyzes an essential metabolic reaction.

Enzyme cofactor

• Acetyl-CoA carboxylase catalyzes the binding of bicarbonate to acetyl-CoA to form malonyl-CoA. Malonyl-CoA is required for the synthesis of fatty acids.
   
• Pyruvate carboxylase is a critical enzyme in gluconeogenesis, the formation of glucose from sources other than carbohydrates, for example, amino acids and fats.
  
• Methylcrotonyl-CoA carboxylase catalyzes an essential step in the metabolism of leucine, an indispensable (essential) amino acid.


• Propionyl-CoA carboxylase catalyzes essential steps in the metabolism of amino acids, cholesterol, and odd chain fatty acids (fatty acids with an odd number of carbon molecules)

Individuals with biotin deficiency are typically healthy before the onset of the biotin-deficient state. Growth and stature are normal. Regardless of the etiology of biotin deficiency, clinical manifestations are essentially the same in all patients; however, the rate of symptom development and the sequence in which symptoms appear greatly vary. Physical manifestations are confined to the skin and hair, central and peripheral nervous systems, and intestinal tract.

Skin and hair: The first signs that develop in biotin deficiency are associated with the skin and hair. Dry skin is a consistent finding and is often associated with seborrheic dermatitis, which can be severe. The skin lesions provide an ideal environment for fungal infections that may be resistant to treatment until the biotin-deficient state is reversed. An erythematous periorofacial macular rash is a common finding. The hair quickly becomes fine and brittle, and total alopecia often develops.

Hearing: Genc et al (2007) performed subjective and objective audiologic tests on 20 children with profound biotinidase deficiency and found that approximately 55% of children with biotinidase deficiency develop sensorineural hearing loss.4 The hearing loss varies in severity, from mild to profound.

Central and peripheral nervous systems: The neurologic signs are multiple and nonspecific. They include mild depression, which may progress to profound lassitude, and, eventually, somnolence. Occasionally, changes in mental status are observed. Generalized muscular pains (myalgias), hyperesthesias, and paresthesias are common findings that occasionally become disabling.

Intestinal tract: Nausea, occasionally severe, is an occasional finding, as is anorexia. These problems are rarely severe enough to significantly interfere with the adequate oral intake of food.

Causes of biotin deficiency include the following:

• Eating raw egg whites: Some mistakenly believe that raw egg-white consumption is the only cause of biotin deficiency. Nonetheless, a diet that contains raw egg whites quickly and almost invariably leads to biotin deficiency.
  
• 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 phenytoin, primidone, and carbamazepine, may lead to biotin deficiency; however, valproic acid therapy does not cause this condition. Some anticonvulsants inhibit biotin transport across the intestinal mucosa. Evidence suggests that these anticonvulsants accelerate biotin catabolism. Therefore, supplemental biotin, in addition to the usual minimum daily requirements, has been suggested for patients who are treated with anticonvulsants that have been linked to biotin deficiency.
  
• 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.

In the body, biotin is found in low concentrations in the brain, liver and muscle tissue. Biotin is utilized to synthesize intracellular carboxylase enzymes and is essential for normal skin and hair growth. The various carboxylase enzymes are important for lipid metabolism and energy production (ATP) via synthesis of oxaloacetate. Alcohol decreases biotin status in the body.