What is the recommended therapeutic dose of biotin for adults and children with biotin deficiency or multiple carboxylase deficiency?

Therapeutic Dose of Biotin

For biotin deficiency or biotinidase deficiency, administer 5-20 mg daily orally in children and adults, with profound biotinidase deficiency requiring lifelong treatment at 5-10 mg/day, while multiple carboxylase deficiency (holocarboxylase synthetase deficiency) may require individualized doses ranging from 10-100 mg/day depending on clinical response. 1, 2

Dosing by Clinical Condition

Biotinidase Deficiency (Profound)

• Standard treatment dose: 5-10 mg daily orally for lifelong therapy 1, 2
• All symptomatic children with profound biotinidase deficiency treated with pharmacological doses of biotin (5-20 mg daily) have shown clinical improvement, with seizures and ataxia resolving within hours to days 1
• Treatment prevents symptom development in presymptomatic children when initiated early 1
• Doses of 10 mg/day or less are sufficient to treat profound biotinidase deficiency 2

Biotinidase Deficiency (Partial)

• Treatment remains controversial but conservative approach recommends treating all individuals with partial deficiency (10-30% of normal activity) to prevent symptoms during metabolic stress 1
• Same dosing as profound deficiency (5-10 mg/day) is appropriate when treatment is elected 1
• Individuals with Km variants and partial activity are at higher risk for symptoms and should be treated 1

Multiple Carboxylase Deficiency (Holocarboxylase Synthetase Deficiency)

• Optimal biotin dose must be assessed individually, ranging from 10-100 mg/day 2
• Some patients respond to 10 mg/day while others require massive doses up to 100 mg/day 2
• Clinical and biochemical response guides dose titration 2

Dosing for Parenteral Nutrition

Infants and Children on Parenteral Nutrition

• Preterm and term infants up to 12 months: 5-8 mcg/kg/day 1
• Children over 12 months: 20 mcg/day for maintenance 1
• For PN-dependent patients with deficiency: IV biotin up to 200 mg/day for 2-3 weeks 3

Adults on Parenteral Nutrition

• Standard maintenance: 60 mcg/day IV (Grade B recommendation) 3
• For malabsorption/short bowel: oral biotin 10 mg/day 3
• IV biotin is reserved exclusively for PN-dependent patients 3

Special Population Dosing

Pregnancy and Lactation

• Pregnancy may require up to 300 mcg/day based on metabolic markers 3, 4
• Breastfeeding requires at least 35 mcg/day orally 3, 4

Renal Replacement Therapy

• Patients on dialysis may require additional biotin beyond standard recommendations 3, 4
• One study used 10 mg daily in three divided doses for uremic neurologic disorders with marked improvement within 3 months 5

Route of Administration

Oral Administration (First-Line)

• Oral biotin is the first-line treatment for biotin deficiency 3
• Nearly complete absorption occurs in humans with normal intestinal function 6
• Malabsorption cases require increased oral doses to 10 mg/day 3

Intravenous Administration

• Reserved exclusively for parenteral nutrition-dependent patients 3
• Up to 200 mg/day IV for 2-3 weeks in severe deficiency 3
• No intramuscular route is recommended in guidelines 3

Safety and Monitoring

Safety Profile

• No upper tolerable limit has been established for biotin 4, 7
• No adverse effects reported with oral or IV doses up to 5 mg/day for prolonged periods 3, 4, 7
• High doses up to 300 mg/day have been used in parenteral nutrition without toxicity 4
• Biotin toxicity is unlikely even at pharmacological doses 7

Critical Monitoring Considerations

• Biotin interferes with laboratory immunoassays, particularly thyroid function tests 8
• Patients taking biotin >5 mg/day should discontinue supplementation for at least 72 hours (preferably 1 week) before laboratory testing 8
• High-dose biotin can cause falsely suppressed TSH and elevated free T4, mimicking Graves' disease 8

Clinical Pitfalls to Avoid

• Never delay treatment in suspected biotinidase deficiency: Delayed commencement results in irreversible neurological damage 2
• Ensure lifelong compliance: Children who failed to comply with biotin therapy developed symptoms within weeks to months 1
• Do not assume partial deficiency is benign: Several children with partial biotinidase deficiency developed symptoms under metabolic stress 1
• Always obtain medication history before interpreting abnormal lab results: Biotin interference can lead to unnecessary interventions for spurious laboratory findings 8