Biotin deficiency

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Biotin deficiency
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Biotin
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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.

Contents

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

Psychological

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

Related Research Articles

<span class="mw-page-title-main">Vitamin K</span> Fat-soluble vitamers

Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation or for controlling binding of calcium in bones and other tissues. The complete synthesis involves final modification of these so-called "Gla proteins" by the enzyme gamma-glutamyl carboxylase that uses vitamin K as a cofactor.

Vitamin B<sub>6</sub> Class of chemically related vitamins

Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.

<span class="mw-page-title-main">Biotin</span> Chemical compound (vitamin B7)

Biotin (also known as vitamin B7 or vitamin H) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. The name biotin, borrowed from the German Biotin, derives from the Ancient Greek word βίοτος (bíotos; 'life') and the suffix "-in" (a suffix used in chemistry usually to indicate 'forming'). Biotin appears as a white crystalline solid that looks like needles.

<span class="mw-page-title-main">Parenteral nutrition</span> Intravenous feeding

Parenteral nutrition (PN) is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding entities or standard pharmaceutical companies. The person receives a nutritional mix according to a formula including glucose, salts, amino acids, lipids and vitamins and dietary minerals. It is called total parenteral nutrition (TPN) or total nutrient admixture (TNA) when no significant nutrition is obtained by other routes, and partial parenteral nutrition (PPN) when nutrition is also partially enteric. It is called peripheral parenteral nutrition (PPN) when administered through vein access in a limb rather than through a central vein as central venous nutrition (CVN).

<span class="mw-page-title-main">Malabsorption</span> Medical condition

Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.

<span class="mw-page-title-main">Short bowel syndrome</span> Medical condition

Short bowel syndrome is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may include bloating, heartburn, feeling tired, lactose intolerance, and foul-smelling stool. Complications can include anemia and kidney stones.

Chromium deficiency is described as the consequence of an insufficient dietary intake of the mineral chromium. Chromium was first proposed as an essential element for normal glucose metabolism in 1959, but its biological function has not been identified. Cases of deficiency were described in people who received all of their nutrition intravenously for long periods of time.

<span class="mw-page-title-main">Biotinidase deficiency</span> Medical condition

Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency.

<span class="mw-page-title-main">3-Methylcrotonyl-CoA carboxylase deficiency</span> Medical condition

3-Methylcrotonyl-CoA carboxylase deficiency also known as 3-Methylcrotonylglycinuria is an inborn error of leucine metabolism and is inherited through an autosomal dominant fashion. 3-Methylcrotonyl-CoA carboxylase deficiency is caused by mutations in the MCCC1 gene, formerly known as MMCA, or the MCCC2 gene, formerly known as MCCB. MCCC1 encodes the a-subunits of 3-methylcrotonyl-CoA carboxylase while MCCC2 encodes the b-subunits. The clinical presentation of 3-Methylcrotonyl-CoA carboxylase deficiency is varied, even within members of the same family.

<span class="mw-page-title-main">Intestinal pseudo-obstruction</span> Medical condition

Intestinal pseudo-obstruction (IPO) is a clinical syndrome caused by severe impairment in the ability of the intestines to push food through. It is characterized by the signs and symptoms of intestinal obstruction without any lesion in the intestinal lumen. Clinical features mimic those seen with mechanical intestinal obstructions and can include abdominal pain, nausea, abdominal distension, vomiting, dysphagia and constipation depending upon the part of the gastrointestinal tract involved.

<span class="mw-page-title-main">Folate deficiency</span> Abnormally low level of folate (vitamin B9) in the body

Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. This may result in a type of anemia in which red blood cells become abnormally large and is a late finding in folate deficiency and folate deficiency anemia is the term given for this medical condition. Signs of folate deficiency are often subtle. Symptoms may include feeling tired, heart palpitations, shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the color of the skin or hair, irritability, and behavioral changes. Temporary reversible infertility may occur. Folate deficiency anemia during pregnancy may give rise to the birth of low weight birth premature infants and infants with neural tube defects.

Pantethine (bis-pantethine or co-enzyme pantethine) is a dimeric form of pantetheine, which is produced from pantothenic acid (vitamin B5) by the addition of cysteamine. Pantethine was discovered by Gene Brown, a PhD student at the time. Pantethine is two molecules of pantetheine linked by a disulfide bridge. Pantetheine is an intermediate in the production of coenzyme A by the body. Most vitamin B5 supplements are in the form of calcium pantothenate, a salt of pantothenic acid, with doses in the range of 5 to 10 mg/day. In contrast, pantethine is sold as a dietary supplement for lowering blood cholesterol and triglycerides at doses of 500 to 1200 mg/day.

<span class="mw-page-title-main">Calcifediol</span> Chemical compound

Calcifediol, also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D3 (abbreviated 25(OH)D3), is a form of vitamin D produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) by the enzyme vitamin D 25-hydroxylase. Calcifediol can be further hydroxylated by the enzyme 25(OH)D-1α-hydroxylase, primarily in the kidney, to form calcitriol (1,25-(OH)2D3), which is the active hormonal form of vitamin D.

Propionyl-CoA is a coenzyme A derivative of propionic acid. It is composed of a 24 total carbon chain and its production and metabolic fate depend on which organism it is present in. Several different pathways can lead to its production, such as through the catabolism of specific amino acids or the oxidation of odd-chain fatty acids. It later can be broken down by propionyl-CoA carboxylase or through the methylcitrate cycle. In different organisms, however, propionyl-CoA can be sequestered into controlled regions, to alleviate its potential toxicity through accumulation. Genetic deficiencies regarding the production and breakdown of propionyl-CoA also have great clinical and human significance.

<span class="mw-page-title-main">Propionyl-CoA carboxylase</span>

Propionyl-CoA carboxylase (EC 6.4.1.3, PCC) catalyses the carboxylation reaction of propionyl-CoA in the mitochondrial matrix. PCC has been classified both as a ligase and a lyase. The enzyme is biotin-dependent. The product of the reaction is (S)-methylmalonyl CoA.

Methylcrotonyl CoA carboxylase is a biotin-requiring enzyme located in the mitochondria. MCC uses bicarbonate as a carboxyl group source to catalyze the carboxylation of a carbon adjacent to a carbonyl group performing the fourth step in processing leucine, an essential amino acid.

Biotinidase, also known as biotinase, is an enzyme that in humans is encoded by the BTD gene.

<span class="mw-page-title-main">Vitamin D deficiency</span> Human disorder

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<span class="mw-page-title-main">Vegan nutrition</span> Nutritional and human health aspects of vegan diets

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<span class="mw-page-title-main">Selenium in biology</span> Use of Selenium by organisms

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References

  1. 1 2 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. 1 2 3 4 5 6 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. Archived (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. 1 2 3 4 "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. 1 2 3 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. 1 2 LLC, HealthMatters io. "Biotin | Healthmatters.io". healthmatters.io. Retrieved 2023-06-19.
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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.
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  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.
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  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.

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