Deficiency biotin

Okey et found that biotin-deficient rats became extremely sensitive to being touched. They lost both their subcutaneous and their visceral fat, and they also failed to store fat in the liver. These workers found that in castrated males implantation of diethylstilbestrol delayed the development 

Sullivan, L. Kolb, and J. Nicholls, Bull. Johns Hopkins Hosp. 70, 17 (1942). 

Despite the appearance of nervous incoordination, there are no signs of damage to the central nervous system, but the muscles show signs of atrophy and in some regions there is necrosis of the fibers. In chicks Couch et al found that biotin deficiency caused shortening of the tibiotarsus, the distal end of which was bent posteriorly. The tarsometatarsus was also shortened, and the distal end was bent medially. In some chicks the wing bones were shortened also. 

Wilson et al and Montagna found that in biotin deficiency in the mouse normal differentiation and function of the skin were impaired. As in the rat, the pilosebaceous units were blocked, and in the sebaceous cells the lipoid droplets were much larger tha normal. Some cells fragmented, and the lipoid phagocytosed by dermal histiocytes. In the dermis mesenchyme cells, in mast cells, and in leucocytes were increased. 

Burt found that, in 236 tissue cultures of embryonic chick neuroblasts, spindle cells, and macrophages, biotin had no growth-stimulating properties. 

More recendy, similar signs of biotin deficiency have been observed in patients receiving totcil parenteral nutrition for prolonged periods, after major resection of the gut. The signs resolve after the provision of biotin, but again there have been no studies of the amounts of biotin required intakes have ranged between 60 to 200 /rg per day (Mock et al., 1985). 

Biotin deficiency, and the functioned deficiency eissociated with lack of holo-carboxylase synthetase (Section 11.2.2.1), or biotinidase (Section 11.2.3.1), causes alopecia (hair loss) and a seedy erythematous dermatitis, especially around the body orifices. The dermatitis is simileu to that seen in zinc euid essential fatty acid deficiency, and is commonly associated with Candida albicans infection. Histology of the skin shows an absence of sebaceous glemds emd atrophy of the hair follicles. The dermatitis is because of impaired metabolism of polyunsaturated fatty acids as a result of low activity of acetyl CoA carboxylase (Section 11.2.1.1). In biotin-deficient experimental animals, provision of supplements of long-chain a 6 polyunsaturated fatty acids prevents the development of skin lesions (Mock et al., 1988a, 1988b Mock, 1991). 

In biotin-deficient rats, the total fatty acid content of the skin is about one-third of normal, and contains a lower than normal proportion of C16 and C18 saturated and unsaturated fatty acids, and a higher than normal proportion of very long-chain fatty acids (especially C24 l and C26 l). There are also increased amounts of odd-chain fatty acids (C15 0 to C29 0), reflecting impaired 

---

Alimentary biotin deficiency is rare. It may, however, occur in patients on long-term parenteral nutrition lacking biotin or in persons who frequently consume raw egg white. Raw egg white contains a biotin-binding glycoprotein, called avidin, which renders biotin biologically unavailable. Pharmacological doses of the vitamin (1-10 mg/d) are then used to treat deficiency symptoms. There are no reports of toxicity for daily oral doses up to 200 mg and daily intravenous doses of up to 20 mg [2]. 

The physiologic sequelae of biotin deficiency are almost unexplored. Severe skin lesions, especially seborrheic dermatitis and Leiner s disease (Erythroderma desquamativum or exfoliative dermatitis), were increased in young infants bom of mothers on a restricted diet low in eggs, livers, and other biotin-rich foods. After biotin administration the lesions healed. There are claims that excess biotin produces a fatty liver characterized by heightened cholesterol content. Choline has no effect in the prevention of biotin-fatty livers (G2, M2). In mice with transplanted tumors, both the tumors and the blood levels of biotin are below normal (R8). More recent studies established a protection with avidin, the biotin-binding fraction of egg white, against tumor formation (K4). More data along these lines are still needed for confirmation. 

Spontaneous biotin deficiency is unlikely to occur as a result of simple dietary restriction, since biotin has high potency, is widely distributed in foods, and is also synthesized in the intestine. The human requirement for biotin is not known, but subjects on a low-biotin diet recovered in 3-5 days, when 75-300 jxg biotin was administered daily (S23, S24). 

M3. Macleod, P. R., and Lardy, H. A., Metabolic functions of biotin. II. The fixation of carbon dioxide by normal and biotin deficient rats. J. Biol. Chem. 179, 733-741 (1949). 

Biotin binds with high af nity (/Cd = 10 M) and specificity to avidin, a protein found in egg white. Since boiling denatures avidin, biotin deficiency only occurs when egg whites are eaten raw. 

Biotin deficiency is characterized by anorexia, nausea, vomiting, glossitis, depression, and dry, scaly dermatitis. Biotin deficiency occurs when avidin, a biotinbinding glycoprotein, is present. Avidin, which is found in raw egg whites, binds the biotin, making it nutritionally unavailable. 

Biotin deficiency can be triggered only experimentally, using diets rich in raw egg white. The latter contains avidin, a 70 kD protein that binds biotin in an inactive form. The deficiency leads to dermatitis and hair loss in rats. 

Patients with complete biotinidase deficiency usually present between 3 and 6 months of age, but severe illness has already been noted at the 2nd and 3rd week of life [9]. On the contrary, patients defined as having profound biotinidase deficiency, who have levels of residual activity as low as 1-3%, may never develop obvious clinical symptoms [17, 33], but may suffer from moderate biotin deficiency when carefully evaluated [25]. Biotin deficiency can be effectively avoided by oral... 

It is important to note that normal plasma biotinidase activity does not exclude that the patient has another cause of multiple carboxylase deficiency (i.e. HCS deficiency or acquired biotin deficiency) [2, 30]. 

Acquired biotin deficiency is extremely rare but may occur in special conditions such as long-term parenteral nutrition without biotin supplementation, short bowel syndrome and after excessive intake of raw egg white, which contains the potent bio-tin-binding protein avidin. The main symptoms are alopecia and skin abnormalities which resolve after administration of biotin [2, 30]. 

Family studies often reveal older siblings or parents with partial or profound biotinidase deficiency [17, 25, 33]. These individuals are usually asymptomatic but may suffer from moderate biotin deficiency [23] and might benefit from biotin therapy. Therefore, all family members should be investigated. 

Biotin deficiency is rare but under laboratory conditions it can be induced by feeding subjects with large amounts of raw egg white which contains the protein, avidin, which has a binding site for the imidazole moiety of biotin, thus making it unavailable. Avidin is denatured by heat and, therefore, biotin binding occurs only in raw egg albumen. Symptoms of biotin deficiency include scaly dermatitis, hair loss, loss of appetite, nausea, hallucinations and depression. 

Rare — None Consumption of large amounts of raw egg whites (which contains e protein, avidin, that binds biotin) can induce a biotin deficiency... 

Biotin (68) is an essential growth factor for many microorganisms, but biotin deficiency is not normally found in man, except perhaps in infants. Its only therapeutic use is in the treatment of seborrhoeic dermatitis of infancy, but it has been tried for the treatment of some forms of baldness. Another heterocyclic sulfur compound, lipoic acid (69), serves as a prosthetic group in several enzymes but it has not been associated with any deficiency disease and has no therapeutic use. 

Biotin 0.15-0.3 mg/day. The discovery that biotin deficiency in young chickens can lead to sudden death resulted in a recommendation to supplement infant formulations with biotin.3 Desthiobiotin, in which the sulfur has been removed and replaced by two hydrogen atoms, can replace biotin in some organisms and appears to lie on one pathway of biosynthesis. b/C Oxybiotin, in which the sulfur has been replaced by oxygen, is active for many organisms and partially active for others. No evidence for conversion to biotin itself has been reported, and oxybiotin may function satisfactorily in at least some enzymes. 

Biotin required for growth and normal function by animals, yeast, and many bacteria is seldom found in deficiency in humans because the intestinal bacteria synthesize it in sufficient quantity to meet requirements. Biotin deficiency does occur, however, 111 animals fed raw whiles of eggs. The egg white contains a protein, avidin, which combines with biotin, and tins complex is not broken down by enzymes of the gastrointestinal tract. Hence, a deficiency develops. 

Bioassay methods include the (1) rat and chick method (growth response after biotin deficiency) (2) microbiological with L arabinosus. Physicochemical methods make use of polarography. 

Ascorbic acid may be required for steroid hormone biosynthesis depleted from adrenal cortex on cortical secretion Biotin adrenocortical insufficiency noted in biotin deficiency... 

Although biotin deficiency is relatively rare, it is characterized by muscle aches, skin rashes, mild depression, slight anemia, and increased serum cholesterol (19,179,180). 

The unusual course of amino acid accumulation in biotin- and pantothenate-deficient cells (Figure 3) also has been found to be markedly influenced by sucrose and other osmotic protectants, as well as by acetate. The course of glutamic acid uptake by biotin-deficient cells in the... 

Figure 6. Effect of sucrose on abnormal glutamate accumulation observed in biotin-deficient cells of L. arabinosus...

Biotin-deficient cells, uptake measured in presence of 0.5M... 

With biotin-deficient cells low concentrations of acetate will substitute for high concentrations of sucrose in restoring uptake to normal levels (22). Biotin stimulates slightly when provided in addition to acetate. Pantothenate-deficient cells respond dramatically to acetate only in the presence of this vitamin. This behavior probably reflects the involvement of coenzyme A in the process which restores a normal accumulation pattern. 

Urinary organic acid analysis is useful for differentiating isolated carboxylase deficiencies from the biotin-responsive multiple carboxylase deficiencies. P-Hydroxyisovalerate is the most common urinary metabolite observed in isolated P-methylcrotonyl-CoA carboxylase deficiency, biotinidase deficiency, biotin holo-carboxylase synthetase deficiency, and acquired biotin deficiency. In addition to P-hydroxy-isovalerate, elevated concentrations of urinary lactate, methylcitrate, and P-hydroxypropionate are indicative of multiple carboxylase deficiency. 

---