This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages)(Learn how and when to remove this template message)
Biotin deficiency is a nutritional disorder which can become serious, even fatal, if allowed to progress untreated. It can occur in people of any age, ancestry, or gender. Biotin is part of the B vitamin family. Biotin deficiency rarely occurs among healthy people because the daily requirement of biotin is low, many foods provide adequate amounts of it, intestinal bacteria synthesize small amounts of it, and the body effectively scavenges and recycles it from bodily waste. However, deficiencies can be caused by consuming raw egg whites over a period of months to years. Egg whites contain high levels of avidin, a protein that binds biotin strongly. When cooked, avidin is partially denatured and binding to biotin is reduced. However one study showed that 30-40% of the avidin activity was still present in the white after frying or boiling. However, cooked egg whites are safer to consume. Genetic disorders such as biotinidase deficiency, multiple carboxylase deficiency, and holocarboxylase synthetase deficiency can also lead to inborn or late-onset forms of biotin deficiency. In all cases – dietary, genetic, or otherwise – supplementation with biotin is the primary method of treatment.
Signs and symptomsEdit
- Rashes including red, patchy ones near the mouth (erythematous periorofacial macular rash)
- Fine and brittle hair
- Hair loss or total baldness (alopecia)
- Birth defects (still being studied)
- Seborrheic dermatitis
- Fungal infections
- 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.
- Protein deficiency: A shortage of proteins involved in biotin homeostasis can cause biotin deficiency. The main proteins involved in biotin homeostasis are HCS, BTD (biotinidase deficiency) and SMVT
- 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 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.
- Smoking: Recent studies suggest that smoking can lead to marginal biotin deficiency because it speeds up biotin catabolism (especially in women).
- Excessive alcohol consumption
- Excessive consumption of antidiuretics or inadequate levels of antidiuretic hormone
- Intestinal malabsorption caused by short bowel syndrome
- Ketogenic diet 
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. 
The most reliable and commonly used methods for determining biotin status in the body are:
In the United States, biotin supplements are readily available without a prescription in amounts ranging from 300 to 10,000 micrograms (30 micrograms is identified as Adequate Intake).
Since biotin is present in many foods at low concentrations, deficiency is rare except in locations where malnourishment is very common. Pregnancy, however, alters biotin catabolism and despite a regular biotin intake, half of the pregnant women in the U.S. are marginally biotin deficient.
- Durance TD (1991). "Residual Avid in Activity in Cooked Egg White Assayed with Improved Sensitivity". Journal of Food Science. 56 (3): 707–709. doi:10.1111/j.1365-2621.1991.tb05361.x.
- Greenway et al. 2011, p. 178.
- Zempleni et al. 2008, p. 715.
- Thompson et al. 2003, p. 315.
- Krause et al. 1982, p. 485.
- Mock et al. 1997, p. 710.
- Hernandez-Vasquez, Alain (2012). "Temporal development of genetic and metabolic effects of biotin deprivation. A search for the optimum time to study a vitamin deficiency". Molecular Genetics and Metabolism. 107 (November 2012): 345–351. doi:10.1016/j.ymgme.2012.09.005. PMID 23010431.
- Yuasa, M (October 2013). "Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet) exaggerates biotin deficiency in mice". Nutrition. 29 (10): 1266–70. doi:10.1016/j.nut.2013.04.011. PMID 24012088.
- Said, H (2011). "Biotin: biochemical, physiological and clinical aspects". Sub-Cellular Biochemistry. Subcellular Biochemistry. 56: 1–19. doi:10.1007/978-94-007-2199-9_1. ISBN 978-94-007-2198-2. PMID 22116691.
- Adhisivam B, Mahto D, Mahadevan S (March 2007). "Biotin responsive limb weakness". Indian Pediatr. 44 (3): 228–30. PMID 17413203.
- Baykal T, Gokcay G, Gokdemir Y, Demir F, Seckin Y, Demirkol M, Jensen K, Wolf B (2005). "Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases". J. Inherit. Metab. Dis. 28 (6): 903–12. doi:10.1007/s10545-005-0161-3. PMID 16435182.
- Boas MA (1927). "The Effect of Desiccation upon the Nutritive Properties of Egg-white". Biochem. J. 21 (3): 712–724.1. doi:10.1042/bj0210712. PMC 1251968. PMID 16743887.
- Dobrowolski SF, Angeletti J, Banas RA, Naylor EW (February 2003). "Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency". Mol. Genet. Metab. 78 (2): 100–7. doi:10.1016/S1096-7192(02)00231-7. PMID 12618081.
- Forbes GM, Forbes A (1997). "Micronutrient status in patients receiving home parenteral nutrition". Nutrition. 13 (11–12): 941–4. doi:10.1016/S0899-9007(97)00334-1. PMID 9433708.
- Genc GA, Sivri-Kalkanoğlu HS, Dursun A, Aydin HI, Tokatli A, Sennaroglu L, Belgin E, Wolf B, Coşkun T (February 2007). "Audiologic findings in children with biotinidase deficiency in Turkey". Int. J. Pediatr. Otorhinolaryngol. 71 (2): 333–9. doi:10.1016/j.ijporl.2006.11.001. PMID 17161472.
- González EC, Marrero N, Frómeta A, Herrera D, Castells E, Pérez PL (July 2006). "Qualitative colorimetric ultramicroassay for the detection of biotinidase deficiency in newborns". Clin. Chim. Acta. 369 (1): 35–9. doi:10.1016/j.cca.2006.01.009. PMID 16480705.
- Greenway FL, Ingram KD, Ravussin E, Hausmann M, Smith SR, Cox L, Tomayko K, Treadwell BV (2011). "Loss of Taste Responds to High-Dose Biotin Treatment". Journal of the American College of Nutrition. 30 (3): 178–181. doi:10.1080/07315724.2011.10719958. PMC 5666569. PMID 21896875.
- Hassan YI, Zempleni J (July 2006). "Epigenetic regulation of chromatin structure and gene function by biotin". J. Nutr. 136 (7): 1763–5. doi:10.1093/jn/136.7.1763. PMC 1479604. PMID 16772434.
- Higuchi R, Mizukoshi M, Koyama H, Kitano N, Koike M (February 1998). "Intractable diaper dermatitis as an early sign of biotin deficiency". Acta Paediatr. 87 (2): 228–9. doi:10.1080/08035259850157732. PMID 9512215.
- Higuchi R, Noda E, Koyama Y, Shirai T, Horino A, Juri T, Koike M (July 1996). "Biotin deficiency in an infant fed with amino acid formula and hypoallergenic rice". Acta Paediatr. 85 (7): 872–4. doi:10.1111/j.1651-2227.1996.tb14171.x. PMID 8819558.
- László A, Schuler EA, Sallay E, Endreffy E, Somogyi C, Várkonyi A, Havass Z, Jansen KP, Wolf B (2003). "Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies". J. Inherit. Metab. Dis. 26 (7): 693–8. doi:10.1023/B:BOLI.0000005622.89660.59. PMID 14707518.
- Mikati MA, Zalloua P, Karam P, Habbal MZ, Rahi AC (November 2006). "Novel mutation causing partial biotinidase deficiency in a Syrian boy with infantile spasms and retardation". J. Child Neurol. 21 (11): 978–81. doi:10.1177/08830738060210110301. PMID 17092467.
- Mock DM (February 1999). "Biotin status: which are valid indicators and how do we know?". J. Nutr. 129 (2S Suppl): 498S–503S. doi:10.1093/jn/129.2.498S. PMID 10064317.
- Mock DM (December 1991). "Skin manifestations of biotin deficiency". Semin Dermatol. 10 (4): 296–302. PMID 1764357.
- Mock DM, Dyken ME (November 1997). "Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants". Neurology. 49 (5): 1444–7. doi:10.1212/wnl.49.5.1444. PMID 9371938.
- Mock DM, Mock NI, Nelson RP, Lombard KA (March 1998). "Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy". J. Pediatr. Gastroenterol. Nutr. 26 (3): 245–50. doi:10.1097/00005176-199803000-00002. PMID 9523856.
- Mock NI, Malik MI, Stumbo PJ, Bishop WP, Mock DM (April 1997). "Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency". Am. J. Clin. Nutr. 65 (4): 951–8. doi:10.1093/ajcn/65.4.951. PMID 9094878.
- Molteno C, Smit I, Mills J, Huskisson J (November 2000). "Nutritional status of patients in a long-stay hospital for people with mental handicap". S. Afr. Med. J. 90 (11): 1135–40. PMID 11196037.
- Möslinger D, Mühl A, Suormala T, Baumgartner R, Stöckler-Ipsiroglu S (December 2003). "Molecular characterisation and neuropsychological outcome of 21 patients with profound biotinidase deficiency detected by newborn screening and family studies". Eur. J. Pediatr. 162 (Suppl 1): S46–9. doi:10.1007/s00431-003-1351-3. PMID 14628140.
- Neto EC, Schulte J, Rubim R, Lewis E, DeMari J, Castilhos C, Brites A, Giugliani R, Jensen KP, Wolf B (March 2004). "Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations". Braz. J. Med. Biol. Res. 37 (3): 295–9. doi:10.1590/S0100-879X2004000300001. PMID 15060693.
- Schulpis KH, Gavrili S, Tjamouranis J, Karikas GA, Kapiki A, Costalos C (May 2003). "The effect of neonatal jaundice on biotinidase activity". Early Hum. Dev. 72 (1): 15–24. doi:10.1016/S0378-3782(02)00097-X. PMID 12706308.
- Thompson, J., Manore M, Sheeshka J (2010). "Nutrients involved in energy metabolism and blood health". In Bennett G, Swieg C, et al. (eds.). Nutrition: A functional Approach. Toronto: Pearson Canada. p. 353. ISBN 9780321740212.
- Velázquez A (1997). "Biotin deficiency in protein-energy malnutrition: implications for nutritional homeostasis and individuality". Nutrition. 13 (11–12): 991–2. doi:10.1016/S0899-9007(97)00345-6. PMID 9433719.
- Weber P, Scholl S, Baumgartner ER (July 2004). "Outcome in patients with profound biotinidase deficiency: relevance of newborn screening". Dev Med Child Neurol. 46 (7): 481–4. doi:10.1111/j.1469-8749.2004.tb00509.x. PMID 15230462.
- Welling DB (August 2007). "Long-term follow-up of hearing loss in biotinidase deficiency". J. Child Neurol. 22 (8): 1055. doi:10.1177/0883073807305789. PMID 17761663.
- Wiznitzer M, Bangert BA (July 2003). "Biotinidase deficiency: clinical and MRI findings consistent with myelopathy". Pediatr. Neurol. 29 (1): 56–8. doi:10.1016/S0887-8994(03)00042-0. PMID 13679123.
- Wolf B (2001). "Disorders of biotin metabolism". In Scriver CR, Beaudet AL, et al. (eds.). The metabolic & molecular bases of inherited disease. New York: McGraw-Hill. pp. 3935–62. ISBN 978-0-07-913035-8.
- Yetgin S, Aytac S, Kalkanoglu S, Coskun T, Ortmann C, Kratz C, Niemeyer C (September 2007). "Biotinidase deficiency and juvenile myelomonocytic leukemia in a Turkish infant of consanguineous parents". Pediatr Hematol Oncol. 24 (6): 453–5. doi:10.1080/08880010701451293. PMID 17710663.
- Zempleni J, Mock DM (March 1999). "Bioavailability of biotin given orally to humans in pharmacologic doses". Am. J. Clin. Nutr. 69 (3): 504–8. doi:10.1093/ajcn/69.3.504. PMID 10075337.