Vitamin B7 deficiency

Background

• Almost all food contain significant quantities of biotin, but it is most found in plants, liver, egg yolk, soybean products, and yeast.
• Daily biotin requirement is low (150-300 ug/d).
• Intestinal flora synthesizes significant quantities of biotin.
• Biotin is recycled in the body and eventually lost in urine and feces.
• Biotin (Vitamin B7) is a cofactor in four major carboxylation reactions

1. Acetyl-CoA Carboxylase (ACC) - Acetyl-CoA to Malonyl-CoA in Fatty Acid Synthesis
2. Pyruvate Carboxylase (PC) - Pyruvate to Oxaloacetate in Gluconeogenesis
3. Propinoyl-CoA Carboxylase (PCC) - Propinoyl-CoA to Methylmalonyl-CoA in Odd Chain Fatty Acid Metabolism
4. Methylcrotonyl CoA Carboxylase (MCC) - 3-Methylcrotonyl CoA to 3-Methylglutaconyl CoA in Leucine Metabolism

• Biotin deficiency is relatively rare. Populations at risk:

1. Long-term Parenteral Nutrition
2. Consumption of raw egg whites (bodybuilders or boxers)

• Secondary biotin deficiency (Multiple Carboxylase Deficiency) is caused by two inherited defects in metabolism:

1. Holocarboxylase Synthetase Deficiency - Autosomal Recessive disorder. Holocarboxylase Synthetase is required to attach biotin to other molecules. Deficiency in this enzyme prevents cells from using Biotin.
2. Biotinidase Deficiency - Biotinidase is required to release Biotin that is bounded to protein.

Clinical Features

• Classical Presentation:
  • Dermatitis - specifically around eyes, nose, mouth
  • Alopecia
  • Enteritis
  • Neurological - including AMS, lethargy, hallucinations, paresthesias
• Holocarboxylase Synthetase Deficiency - presents in the first week of life with:
  • lethargy
  • hypotonia
  • vomiting
• Biotinidase Deficiency - presents later in life with:
  • dermatitis
  • neurological symptoms - ataxia, seizures, myoclonus, nystagmus
  • ketoacidosis

Differential Diagnosis

• DDx involves genetic disorders with impaired carboxylation.
  • Biotinidase Deficiency (see above)
  • Holocarboxylase Synthetase Deficiency (see above)
  • Carnitine Deficiency
  • Methylmalonic Acidemia
  • Propionic Acidemia
  • Pyruvate Carboxylase Deficiency
• Starvation
• Medication Use - Antibiotics or Anti-convulsants
• Other vitamin deficiencies:

Vitamin deficiencies

• Vitamin A deficiency
• Vitamin B deficiencies
  • Vitamin B1 deficiency (Thiamine)
    • Beriberi
    • Wernicke-Korsakoff syndrome
  • Vitamin B3 deficiency (Pellagra)
  • Vitamin B9 deficiency (Folate)
  • Vitamin B12 deficiency
• Vitamin C deficiency (Scurvy)
• Vitamin D deficiency (Rickets)
• Vitamin E deficiency
• Vitamin K deficiency

Evaluation

• Diagnosis is primarily clinical. Routine serum chemistry panel should be checked.
• Other Laboratory Studies
  • Newborn Screening
  • Serum Biotinidase Activity decreased
  • Serum Ammonia Levels increased
  • Plasma Carnitine
  • Quantitative Amino Acid levels
  • Urine B-Hydroxyisoverlate decreased
  • Urine Biotin decreased
  • Urine Ketones increased

Management

• Supplementation of Biotin. Dosage is debated:
  • 150 ug intramuscular injection suggested
  • 5-20 mg/dl have also been used

• Stop consumption of raw eggs.
• Stop anti-convulsant or anti-biotic use.

Disposition

• Follow-up with primary care provider or referral to genetic specialist.