Biotin deficiency

Biotin deficiency
Biotin
Classification and external resources
Specialty
ICD-10	E53.8
ICD-9-CM	266.2
eMedicine	ped/238
Patient UK	Biotin deficiency

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 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 from bodily waste. However, deficiencies can be caused by consuming raw egg whites over a period of months to years. Egg whites contain high levels of avidin, a protein that binds biotin strongly. When cooked, avidin is partially denatured and binding to biotin is reduced. However one study showed that 30-40% of the avidin activity was still present in the white after frying or boiling. Hence excessive cooked egg white consumption could possibly cause biotin deficiency. Genetic disorders such as Biotinidase deficiency, Multiple carboxylase deficiency, and Holocarboxylase synthetase deficiency can also lead to inborn or late-onset forms of biotin deficiency. In all cases – dietary, genetic, or otherwise – supplementation with biotin is the primary method of treatment.

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.

Signs and symptoms

• Rashes including red, patchy ones near the mouth (erythematous periorofacial macular rash)
• Fine and brittle hair
• Hair loss or total baldness (alopecia)
• Anemia
• Birth Defects (still being studied)
• Seborrheic dermatitis
• Fungal infections

Psychological

• Hallucinations
• Lethargy
• Anorexia
• Mild depression, which may progress to profound fatigue and, eventually, to somnolence
• Generalized muscular pains (myalgias)
• Paresthesias

Causes

1. 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.
2. 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) and SMVT
3. 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.
4. Severe Malnourishment
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.
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.
7. Pregnancy

Potential Causes

1. Smoking: Recent studies suggest that smoking can lead to marginal biotin deficiency because it speeds up biotin catabolism (especially in women).
2. Excessive alcohol consumption
3. Excessive consumption of antidiuretics or inadequate levels of antidiuretic hormone
4. Intestinal malabsorption caused by short bowel syndrome
5. Ketogenic Diet

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
• activity of propionyl-CoA carboxylase in lymphocytes

Treatment

In the United States biotin supplements are readily available without a prescription in amounts ranging from 1,000 to 10,000 micrograms (30 micrograms is identified as Adequate Intake).

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, Holocarboxylase synthetase deficiency, and Multiple carboxylase deficiency, 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