Biotin deficiency

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 of either sex. 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 in the kidneys during production of urine.

Biotin deficiency
Biotin
Specialty	Endocrinology

Genetic disorders such as multiple carboxylase deficiency (MCD) (which includes biotinidase deficiency and holocarboxylase synthetase deficiency)^[1] can also lead to inborn or late-onset forms of biotin deficiency.^[2] In all cases – dietary, genetic, or otherwise – supplementation with biotin is the primary (and usually only)^[3] method of treatment.^[1][4] The prognosis for congenital MCD is good if biotin supplementation is begun quickly after birth and carried on throughout the patients life.^[5]

The average dietary intake of biotin ranges between 35 and 70 micrograms/day in the western population.^[2]

Signs and symptoms

Physical

• Rashes including red, patchy ones near openings^[6] (e.g. erythematous periorofacial macular rash)^[7]
• Hair loss (alopecia)^[8]
• Conjunctivitis^[8]
• Brittle nails^[6]
• Generalized muscular pains (myalgia)^[9]
• Paresthesias (pins and needles)^[10] and numbness^[8] in the extemities

Psychological

• Hallucinations^[6]
• Lethargy^[6]
• Mild depression^[11]
• Fatigue, drowsiness^[12] and somnolence^[9]

Causes

1. Total parenteral nutrition without biotin supplementation: Several cases^[13] 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.^[2]
2. Protein deficiency (not certain): A shortage of proteins involved in biotin homeostasis can cause biotin deficiency. The main problems involved in biotin homeostasis are HCS, BTD (biotinidase deficiency) and SMVT^[14]
3. 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.^[15] 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.
4. Severe malnourishment^[16][2]
5. 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.^[2][17]
6. 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.^[18]

Potential causes

1. Smoking: Recent studies^[14] suggest that smoking can lead to marginal biotin deficiency because it speeds up biotin catabolism (especially in women).^[19]
2. Excessive alcohol consumption^[20] (causes a significant reduction in plasma biotin levels)
3. Excessive consumption of antidiuretics or inadequate levels of antidiuretic hormone^[21]
4. Intestinal malabsorption caused by short bowel syndrome^[22]

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.^[23]

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.^[24]

Treatment

In the United States, biotin supplements are readily available without a prescription^[25] in amounts ranging from 300 to 10,000 micrograms.^[26] 30 micrograms daily is identified as Adequate Intake for men and women 19 years and older. 35 micrograms daily is required for lactating women.^[27]

Most healthy individuals meet these recommended intakes, however many still take up to 500 to 1,000 micrograms of biotin daily.^[28]

Epidemiology

Deficiency is rare^[2] in locations where egg-white enriched or ketogenic diets are common.^[29] Pregnancy, however, alters biomarkers of biotin^[30] and despite a regular biotin intake, approximately half of the pregnant women in the U.S. are marginally biotin deficient.^[14]

See also

• Biotinidase deficiency
• Holocarboxylase synthetase deficiency
• Multiple carboxylase deficiency

References

1. Chinese Medical Association, Division of Biochemistry and Metabolism; Chinese Association for Maternal and Child Health, Division of Genetics and Metabolism; Rare Diseases Committee of Beijing Medical Association, Division of Genetics and Metabolism (2022-02-25). "Expert consensus on screening, diagnosis and treatment of multiple carboxylase deficiency". Zhejiang da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences. 51 (1): 129–135. doi:10.3724/zdxbyxb-2022-0164. ISSN 1008-9292. PMC 9109762. PMID 35576117.
2. Saleem, Fatima; Soos, Michael P. (2023), "Biotin Deficiency", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31613531, retrieved 2023-06-19
3. "Multiple Carboxylase Deficiency" (PDF). Texas Department of State Health Services. 2023-06-19. (PDF) from the original on 2023-06-19. Retrieved 2023-06-19.
4. "Biotinidase Deficiency - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2023-06-19.
5. Baumgartner, E. R.; Suormala, T. (1997). "Multiple carboxylase deficiency: inherited and acquired disorders of biotin metabolism". International Journal for Vitamin and Nutrition Research. 67 (5): 377–384. ISSN 0300-9831. PMID 9350481.
6. "Office of Dietary Supplements - Biotin". ods.od.nih.gov. Retrieved 2023-06-19.
7. Rajendiran, Ashwin; Sampath, Sowmya (2011-09-30). "Biotinidase deficiency – clinching the diagnosis rapidly can make all the difference!". BMJ Case Reports. 2011: bcr0720114494. doi:10.1136/bcr.07.2011.4494. ISSN 1757-790X. PMC 3185397. PMID 22679321.
8. Trüeb, Ralph M (2016). "Serum Biotin Levels in Women Complaining of Hair Loss". International Journal of Trichology. 8 (2): 73–77. doi:10.4103/0974-7753.188040. ISSN 0974-7753. PMC 4989391. PMID 27601860.
9. LLC, HealthMatters io. "Biotin | Healthmatters.io". healthmatters.io. Retrieved 2023-06-19.
10. "Biotin (vitamin B7) for hair growth: Uses, sources, health benefits". www.medicalnewstoday.com. 2017-10-18. Retrieved 2023-06-19.
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12. Abed, Ali-Reza; Abed, Alireza; Banafshe, Hamid Reza; Malekabad, Ebadallah Shiri; Gorgani-firuzjaee, Sattar; Dadashi, Ali-Reza (2021-05-12). "Effect of biotin supplementation on neuropathic pain induced by chronic constriction of the sciatic nerve in the rat". Research in Pharmaceutical Sciences. 16 (3): 250–259. doi:10.4103/1735-5362.314823. ISSN 1735-5362. PMC 8216157. PMID 34221058.
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17. Hayashi, Atsushi; Mikami, Yohei; Miyamoto, Kentaro; Kamada, Nobuhiko; Sato, Toshiro; Mizuno, Shinta; Naganuma, Makoto; Teratani, Toshiaki; Aoki, Ryo; Fukuda, Shinji; Suda, Wataru; Hattori, Masahira; Amagai, Masayuki; Ohyama, Manabu; Kanai, Takanori (2017-08-15). "Intestinal Dysbiosis and Biotin Deprivation Induce Alopecia through Overgrowth of Lactobacillus murinus in Mice". Cell Reports. 20 (7): 1513–1524. doi:10.1016/j.celrep.2017.07.057. ISSN 2211-1247. PMID 28813664.
18. Mikati, Mohamad A.; Zalloua, Pierre; Karam, Pascale; Habbal, Mohamad-Zuheir; Rahi, Amal C. (November 2006). "Novel mutation causing partial biotinidase deficiency in a Syrian boy with infantile spasms and retardation". Journal of Child Neurology. 21 (11): 978–981. doi:10.1177/08830738060210110301. ISSN 0883-0738. PMID 17092467. S2CID 26189957.
19. Sealey, Wendy M; Teague, April M; Stratton, Shawna L; Mock, Donald M (October 2004). "Smoking accelerates biotin catabolism in women". The American Journal of Clinical Nutrition. 80 (4): 932–935. doi:10.1093/ajcn/80.4.932. ISSN 0002-9165. PMC 1450014. PMID 15447901.
20. Subramanya, Sandeep B.; Subramanian, Veedamali S.; Kumar, Jeyan S.; Hoiness, Robert; Said, Hamid M. (March 2011). "Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms". American Journal of Physiology. Gastrointestinal and Liver Physiology. 300 (3): G494–G501. doi:10.1152/ajpgi.00465.2010. ISSN 0193-1857. PMC 3064116. PMID 21148397.
21. Hoffman, Kristine (January 2015). "When Vitamin And Nutritional Deficiencies Cause Skin And Nail Changes". www.hmpgloballearningnetwork.com. Retrieved 2023-06-19.
22. Khalidi, N.; Wesley, J. R.; Thoene, J. G.; Whitehouse, W. M.; Baker, W. L. (1984). "Biotin deficiency in a patient with short bowel syndrome during home parenteral nutrition". Journal of Parenteral and Enteral Nutrition. 8 (3): 311–314. doi:10.1177/0148607184008003311. hdl:2027.42/141489. ISSN 0148-6071. PMID 6429370.
23. Said, H (2012). "Biotin: Biochemical, Physiological and Clinical Aspects". Water Soluble Vitamins. Subcellular Biochemistry. Vol. 56. pp. 1–19. doi:10.1007/978-94-007-2199-9_1. ISBN 978-94-007-2198-2. PMID 22116691.
24. Eng, Wei Kay; Giraud, David; Schlegel, Vicki L.; Wang, Dong; Lee, Bo Hyun; Zempleni, Janos (2013-07-28). "Identification and assessment of markers of biotin status in healthy adults". The British Journal of Nutrition. 110 (2): 321–329. doi:10.1017/S0007114512005065. ISSN 0007-1145. PMC 4743878. PMID 23302490.
25. "Biotin (Oral Route) Description and Brand Names - Mayo Clinic". www.mayoclinic.org. Retrieved 2023-06-19.
26. Katzman, Brooke M.; Lueke, Alan J.; Donato, Leslie J.; Jaffe, Allan S.; Baumann, Nikola A. (2018-09-01). "Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department". Clinical Biochemistry. 60: 11–16. doi:10.1016/j.clinbiochem.2018.07.004. ISSN 0009-9120. PMID 30036510. S2CID 51710689.
27. Avenue, 677 Huntington; Boston; Ma 02115 (2019-07-24). "Biotin – Vitamin B7". The Nutrition Source. Retrieved 2023-06-19.{{cite web}}: CS1 maint: numeric names: authors list (link)
28. Patel, Deepa P.; Swink, Shane M.; Castelo-Soccio, Leslie (August 2017). "A Review of the Use of Biotin for Hair Loss". Skin Appendage Disorders. 3 (3): 166–169. doi:10.1159/000462981. ISSN 2296-9195. PMC 5582478. PMID 28879195.
29. Dakshinamurti, Krishnamurti; Dakshinamurti, Shyamala; Czubryt, Michael P. (2019), Preedy, Victor R.; Patel, Vinood B. (eds.), "Effects of Biotin Deprivation and Biotin Supplementation", Handbook of Famine, Starvation, and Nutrient Deprivation: From Biology to Policy, Cham: Springer International Publishing, pp. 1613–1633, doi:10.1007/978-3-319-55387-0_73, ISBN 978-3-319-55387-0, retrieved 2023-06-19
30. Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A (December 2014). "Pregnancy and Lactation Alter Biomarkers of Biotin Metabolism in Women Consuming a Controlled Diet123". The Journal of Nutrition. 144 (12): 1977–1984. doi:10.3945/jn.114.194472. ISSN 0022-3166. PMC 4230210. PMID 25122647.

Possible references

• 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. S2CID 22277450.
• 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.
• 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.
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External links

• GeneReviews/NCBI/NIH/UW entry on Biotinidase deficiency
• OMIM entries on Biotinidasa deficiency