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Biotin Deficiency

Deficiency of Biotin

One of the essential vitamins is biotin, a cofactor for four enzymes with roles in intermediate metabolism. Biotin deficiency can be acquired: it can be due to inadequate biotin intake during parenteral nutrition, or due to consumption of raw egg white. Biotin deficiency can also be due to genetic defects in proteins that play an important role in biotin homeostasis.


Presentation

Biotin deficiency can develop under a variety of circumstances. Within weeks to months, people on total parenteral nutrition lacking biotin, or infants fed on formula lacking biotin will start to display thinning or loss of hair and will develop scaly skin rashes, usually around the mouth, nose, and eyes. Similar symptoms develop in people who eat raw egg white for prolonged duration, which contains avidin, a protein that binds to biotin strongly. Neurological symptoms in adults include lethargy, depression, seizures, ataxia, and paresthesia of the hands and feet. Infants are also lethargic and have developmental problems. Other symptoms are acidosis and organic aciduria.

A milder form of biotin deficiency may develop because of increased catabolism of biotin. This may be caused by treatment with anticonvulsants [1] or by smoking [2]. These are marginal effects, without the signs of overt deficiency. Pregnancy and lactation increase the demand for biotin [3] and thus, may also result in marginal biotin deficiency [4]. However small degree of deficiency is also of crucial importance, as even marginal biotin deficiency can have teratogenic effects according to animal studies [4] [5]. Chronic biotin deficiency may also develop in preterm infants fed on mother’s milk [6].

Biotin deficiency can also develop in people with genetic conditions affecting enzymes responsible for the metabolism of biotin [7]. These include two vitamin transporters, which facilitate the movement of biotin into cells; a holocarboxylase synthetase, which binds biotin covalently to its target proteins; and biotinidase, which liberates free biotin from biotin containing peptides and biotinyl-lysine in the gastrointestinal system, and thereby plays a central role in the recycling and absorption of biotin. Biotinidase deficiency is an autosomal recessive condition. People with biotinidase defects present with symptoms similar to those of acquired biotin deficiency, but in addition have a hearing and vision loss [7] [8].

Malnutrition
  • Abstract Several of the clinical and biochemical manifestations of biotin deficiency also occur in severe protein-energy malnutrition (PEM).[ncbi.nlm.nih.gov]
  • Ziboh , Malnutrition‐Associated Rash of Cystic Fibrosis , Pediatric Dermatology , 17 , 5 , (337-347) , (2001) .[doi.org]
  • Severe malnutrition due to poverty, ketogenic diet or eating foods very low in the vitamin may cause low levels of the vitamin B7 in the plasma.[allnutriments.blogspot.com]
  • Protein-energy malnutrition can affect wound healing.[podiatrytoday.com]
  • "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).[en.wikipedia.org]
Turkish
  • Abstract Here, a case is presented with two rare genetic disorders, biotinidase deficiency and juvenile myelomonocytic leukemia, in a Turkish infant.[doi.org]
  • . , et al: Novel mutations cause biotinidase deficiency in Turkish children . J Inherit Metab Dis 2000 ; 23: 120 — 128 .[doi.org]
  • "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).[en.wikipedia.org]
Rigor
  • Abstract To date, marginal, asymptomatic biotin deficiency has been successfully induced experimentally by the use of labor-intensive inpatient designs requiring rigorous dietary control.[ncbi.nlm.nih.gov]

Workup

Bioassays have been developed and used for the determination of biotin levels in blood. However, plasma concentrations measured by these methods are often not reliable indicators of the biotin status, partly because the assays may not distinguish between biotin and its inactive metabolites [4]. The secondary effects of biotin deficiency can be measured through assessing the activities of biotin-dependent enzymes [4] [9]. Biotin is an essential cofactor for two acetyl-CoA carboxylases, pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase [7]. Decreased activity of methylcrotonyl-CoA carboxylase leads to the accumulation of methylcrotonyl-CoA and to its conversion to 3-hydroxyisovaleric acid, which can be measured in the urine. The concentration of 3-hydroxyisovaleric acid is a good indicator of the biotin status [4] [9].

Recently a new liquid chromatography tandem mass spectrometry method has been developed for the measurement of the carnitine-bound substrate/product pairs for the biotin-dependent enzymes [9]. Thus, this method affords the determination of the activity of several biotin-dependent enzymes and therefore provides a more robust assessment of the biotin status in cases of marginal biotin deficiency (such as may occur in pregnancy) than assays relying on just one enzyme activity.

Biotidinase activity can be measured from blood samples on paper discs, or in serum using colorimetric assays. Children with less than ten percent of normal serum enzyme activity present with severe biotinidase deficiency [10].

Other tests may include urine ketone and organic acid levels, and serum ammonia levels.

Suppression
  • This suppressed proliferation of mesenchymal cells may delay or inhibit the growth of palatal processes in embryos and thus it may partially contribute to the mechanisms for cleft palate induction.[ncbi.nlm.nih.gov]
Staphylococcus Aureus
  • Abstract Staphylococcus aureus isolates from humans and other animals were grown in biotin assay medium containing 12 mug of biotin per liter and compared to isolates from the same sources grown concurrently in medium containing adequate biotin.[ncbi.nlm.nih.gov]

Treatment

  • Biotin-deficient cells exhibited smaller activities of the apoptotic enzyme caspase-3 in response to treatment with tumor necrosis factor alpha, and decreased cell death in response to serum starvation compared to biotin-supplemented cells.[ncbi.nlm.nih.gov]
  • With treatment, patients may run a normal lifestyle and have an excellent prognosis [5]. Diagnosis is made by a blood test. Treatment is by oral biotin supplements.[nutrientsreview.com]
  • If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.[babysfirsttest.org]
  • Pre-treatment EEG may show characteristic changes but may be normal after treatment. Management [ 1, 9 ] All patients with less than 10% biotinidase (BTD) activity should receive biotin supplements.[patient.info]
  • Diagnosis Signs, lesions, response to treatment/prevention. Differentiate from pantothenic acid deficiency (skin lesions). Treatment Addition of biotin in feed or water.[thepoultrysite.com]

Prognosis

  • The disorder has a good prognosis if biotin therapy is introduced early. If not, it can result in irreversible damage to the central nervous system and early death from metabolic acidosis.[ncbi.nlm.nih.gov]
  • With treatment, patients may run a normal lifestyle and have an excellent prognosis [5]. Diagnosis is made by a blood test. Treatment is by oral biotin supplements.[nutrientsreview.com]
  • Prognosis [ 1 ] If the condition is treated promptly, no symptoms may arise. Delayed treatment may result in neurological complications, including mental retardation, seizures and coma.[patient.info]
  • The prognosis of the two above mentioned disorders (enzyme deficiencies) is usually good if biotin supplementation is started early and continued for life (45). Authored by Dr Peter Engel in 2010, reviewed and revised by Ines Warnke on 28.06.2017[nutri-facts.org]

Etiology

  • There is evidence that impaired fatty acid metabolism secondary to reduced activities of the biotin-dependent carboxylases (especially acetyl-CoA carboxylase) plays an etiologic role in the dermatologic manifestations of biotin deficiency.[ncbi.nlm.nih.gov]
  • Biotin deficiency due to a defect in biotin transport has also been described. [25] Regardless of the etiology of biotin deficiency, clinical manifestations are similar.[emedicine.com]
  • [Values of tandem mass spectrometry in etiologic diagnosis of cerebral developmental retardation]. Zhonghua Er Ke Za Zhi 2007;45:932–6 Shevell M, Ashwal S, Donley D, et al.[bestbets.org]

Epidemiology

  • Epidemiology Incidence is less than 1 in 60,000 babies - no more than 12 cases per year. [ 3 ] The carrier frequency in the general population is 1 in 120. [ 4 ] Presentation [ 1, 2 ] Usually presents aged 1 week to 2 years (earlier-onset carboxylase[patient.info]
  • Epidemiology [ edit ] Since biotin is present in many foods at low concentrations, deficiency is rare except in locations where malnourishment is very common.[en.wikipedia.org]
Sex distribution
Age distribution

Prevention

  • In summary, to prevent biotin deficiency, biotin should be added to the Japanese amino acid formula.[ncbi.nlm.nih.gov]
  • Prevention Supplementation of diets with biotin - naturally present in many raw materials, has very low bioavailability.[thepoultrysite.com]
  • Restoring biotin to the biotin-deficient medium prevented the above changes. Old cells were more susceptible to biotin shortage than young cells.[ncbi.nlm.nih.gov]
  • Medications Certain medicines may prevent your body from absorbing vitamins correctly. These medications include antibiotics and anti-seizure drugs.[healthline.com]
  • Symptoms of biotinidase deficiency are resolved or prevented with oral biotin supplementation and as such newborn screening is performed to prospectively identify affected individuals prior to the onset of symptoms.[ncbi.nlm.nih.gov]

References

Article

  1. Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology. 1997;49:1444–1447.
  2. Sealey WM, Teague AM, Stratton SL, Mock DM. Smoking accelerates biotin catabolism in women. Am J Clin Nutr. 2004 Oct;80(4):932-935.
  3. Perry CA, West AA, Gayle A, et al. Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet. J Nutr. 2014 Dec;144(12):1977-1984.
  4. Mock DM, Stadler DD, Stratton SL, Mock NI. Biotin status assessed longitudinally in pregnant women. J Nutr. 1997;127:710–716.
  5. Mock DM. Marginal biotin deficiency is common in normal human pregnancy and is highly teratogenic in mice. J Nutr. 2009 Jan;139(1):154-157.
  6. Tokuriki S, Hayashi H, Okuno T, et al. Biotin and carnitine profiles in preterm infants in Japan. Pediatr Int. 2013 Jun;55(3):342-345.
  7. Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab. 2008 November 1; 3(6):715–724.
  8. Baykal T, Gokcay G, Gokdemir Y, et al. Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases. J Inherit Metab Dis. 2005;28(6):903-912.
  9. Bogusiewicz A, Horvath TD, Stratton SL, Mock DM, Boysen G. Measurement of acylcarnitine substrate to product ratios specific to biotin-dependent carboxylases offers a combination of indicators of biotin status in humans. J Nutr. 2012;142(9):1621-1625.
  10. Neto EC, Schulte J, Rubim R, et al. Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations. Braz J Med Biol Res. 2004 Mar. 37(3):295-299.

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Last updated: 2018-06-22 06:52