- Almost all food contain significant quantities of biotin, but it is most found in plants, liver, egg yolk, soybean products, and yeast.
- Daily biotin requirement is low (150-300 ug/d).
- Intestinal flora synthesizes significant quantities of biotin.
- Biotin is recycled in the body and eventually lost in urine and feces.
Cofactor in four major carboxylation reactions
- Acetyl-CoA Carboxylase (ACC) - Acetyl-CoA to Malonyl-CoA in Fatty Acid Synthesis
- Pyruvate Carboxylase (PC) - Pyruvate to Oxaloacetate in Gluconeogenesis
- Propinoyl-CoA Carboxylase (PCC) - Propinoyl-CoA to Methylmalonyl-CoA in Odd Chain Fatty Acid Metabolism
- Methylcrotonyl CoA Carboxylase (MCC) - 3-Methylcrotonyl CoA to 3-Methylglutaconyl CoA in Leucine Metabolism
Biotin deficiency risk factors
- Long-term Parenteral Nutrition
- Consumption of raw egg whites (bodybuilders or boxers)
Secondary biotin deficiency (Multiple Carboxylase Deficiency)
is caused by two inherited defects in metabolism:
- Holocarboxylase Synthetase Deficiency - Autosomal Recessive disorder. Holocarboxylase Synthetase is required to attach biotin to other molecules. Deficiency in this enzyme prevents cells from using Biotin.
- Biotinidase Deficiency - Biotinidase is required to release Biotin that is bounded to protein.
- Classical Presentation:
- Dermatitis - specifically around eyes, nose, mouth
- Neurological - including AMS, lethargy, hallucinations, paresthesias
- Holocarboxylase Synthetase Deficiency - presents in the first week of life with:
- Biotinidase Deficiency - presents later in life with:
- neurological symptoms - ataxia, seizures, myoclonus, nystagmus
- DDx involves genetic disorders with impaired carboxylation.
- Biotinidase Deficiency (see above)
- Holocarboxylase Synthetase Deficiency (see above)
- Carnitine Deficiency
- Methylmalonic Acidemia
- Propionic Acidemia
- Pyruvate Carboxylase Deficiency
- Medication Use - Antibiotics or Anti-convulsants
- Other vitamin deficiencies:
- Diagnosis is primarily clinical. Routine serum chemistry panel should be checked.
- Other Laboratory Studies
- Newborn Screening
- Serum Biotinidase Activity decreased
- Serum Ammonia Levels increased
- Plasma Carnitine
- Quantitative Amino Acid levels
- Urine B-Hydroxyisoverlate decreased
- Urine Biotin decreased
- Urine Ketones increased
- Supplementation of Biotin. Dosage is debated:
- 150 ug intramuscular injection suggested
- 5-20 mg/dl have also been used
- Stop consumption of raw eggs.
- Stop anti-convulsant or anti-biotic use.
- Follow-up with primary care provider or referral to genetic specialist.