Biotin deficiency is a rare 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

Biotin

Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...

 deficiency rarely occurs among healthy people because the daily requirement of biotin is low, many foods provide adequate amounts of it, intestinal bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 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 white

Egg white

Egg white is the common name for the clear liquid contained within an egg. In chickens it is formed from the layers of secretions of the anterior section of the hen's oviduct during the passage of the egg. It forms around either fertilized or unfertilized egg yolks...

s over a period of months to years. Egg whites contain high levels of avidin

Avidin

Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...

, a protein that binds biotin strongly. When cooked, avidin is partially denatured

Denaturation (biochemistry)

Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...

 and becomes somewhat non-toxic. A recent study found that activity in fried, poached and boiled (2 min) egg white was 33, 71 and 40% of the activity in raw egg white respectively.

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

Catabolism

Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...

, gluconeogenesis, and fatty acid metabolism. Biotin

Biotin

Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...

 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

Biotinidase

Biotinidase also known as BTD is an enzyme that in humans is encoded by the BTD gene.- Function :This enzyme allows the body to use and to recycle the B vitamin biotin, sometimes called vitamin H. Biotinidase extracts biotin from food because the body needs biotin in its free, unattached form...

 (BTD), and the protein ligase holocarboxylase synthetase. When any of these regulatory factors are inhibited, biotin deficiency could occur.

Clinical Symptoms

• Rashes including red, patchy ones near the mouth (erythematous periorofacial macular rash)
• Fine and brittle hair
• Hair loss or total baldness (alopecia
  Alopecia
  Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
  
  )
• Anemia
  Anemia
  Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
  
  
• Birth Defects(Still being studied)
• Seborrheic dermatitis
• Fungal infections

Psychological Symptoms

• Hallucinations
• Lethargy
• Anorexia
  Anorexia
  - Eating conditions :* Anorexia , the symptom of poor appetite whatever the cause* Anorexia nervosa, an eating disorder of excessive weight loss and usually undue concern about body shape...
  
  
• Mild depression
  Depression (mood)
  Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
  
  , which may progress to profound lassitude and, eventually, to somnolence
  Somnolence
  Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
  
  
• Generalized muscular pains (myalgias)
• paresthesias

Confirmed Causes

1. Eating raw egg whites: Some mistakenly believe that raw egg-white consumption is the only cause of biotin deficiency. Nonetheless, a diet that contains an excess of raw egg whites quickly and almost invariably leads to biotin deficiency.
2. 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.
3. 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
   Biotinidase deficiency
   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....
   
   ) and SMVT
4. Anticonvulsant therapy: Prolonged use of certain drugs, especially 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. Therefore, supplemental biotin, in addition to the usual minimum daily requirements, has been suggested for patients who are treated with anticonvulsants that have been linked to biotin deficiency.
5. Severe Malnourishment
6. 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.
7. Genetic mutation: Mikati et al (2006) reported a case of partial biotinidase deficiency
   Biotinidase deficiency
   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....
   
    (plasma biotinidase level of 1.3 nm/min/mL) in a 7-month-old boy.8 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.
8. Pregnancy

Potential Causes

1. Smoking: Recent studies suggest that smoking can lead to marginal biotin deficiency because it speeds up biotin catabolism
   Catabolism
   Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
   
    (especially in women).
2. Excessive alcohol consumption
3. Intestinal malabsorption caused by short bowel syndrome
   Short bowel syndrome
   Short bowel syndrome is a malabsorption disorder caused by the surgical removal of the small intestine, or rarely due to the complete dysfunction of a large segment of bowel. Most cases are acquired, although some children are born with a congenital short bowel...
   
   

Diagnosis

The most reliable and commonly used methods for determining biotin status in the body are:

• excretion of 3-hydroxyisovaleric acid and biotin in urine
  Urine
  Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
  
  
• activity of propionyl-CoA carboxylase in lymphocytes

Treatment

Biotin supplements can be taken in pill form. The diet can also be altered to include more cows’ milk and liver, which are good sources of biotin. If overconsumption of raw egg whites is responsible, a change in diet may be appropriate.

Epidemiology

Since biotin is 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.

See also

• Biotinidase deficiency
  Biotinidase deficiency
  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....
  
  , Holocarboxylase synthetase deficiency
  Holocarboxylase synthetase deficiency
  Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on...
  
  , and Multiple carboxylase deficiency
  Multiple carboxylase deficiency
  Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation enzymes.The deficiency can be in biotinidase or holocarboxylase synthetase.These conditions respond to biotin.Forms include:...
  
  , in which biotin is required in very high amounts to correct underlying genetic problems with biotin-related enzymes.

External links

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