Also Known as
BIOT, BTD deficiency, late-onset biotin responsive multiple carboxylase deficiency
How it is inherited

Biotinidase deficiency is inherited in an autosomal recessive pattern. Normally a person has two functional BTD genes. In people with biotinidase deficiency, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with biotinidase deficiency typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.

Symptoms in carriers

Carriers of biotinidase deficiency do not typically have symptoms.

Symptoms

If treated prior to the onset of symptoms, most people with biotinidase deficiency do not have symptoms. If untreated, symptoms may appear between 1 and 10 weeks of age. The symptoms are variable and may include seizures, hypotonia (low muscle tone), developmental delay, hearing loss, vision problems, ataxia (poor balance and coordination), skin rashes, hair loss and candidiasis (fungal infection). If treated prior to onset, symptoms will not appear in most cases.

Newborn screening
  • Incidence: The overall incidence is approximately 1 in 60,000.
  • New York State Method of Screening (First Tier): Screening for biotinidase deficiency is accomplished by a qualitative colorimetric assay.
  • Second Tier Screening: None
  • Testing can be affected by: False positive results can be caused by improper specimen collection or drying, including samples placed in plastic prior to drying, exposure to heat and humidity or delayed transit. Impaired liver function and prematurity can also cause a false positive result. A false negative may be caused by the administration of antibiotic or blood transfusion.
  • Interpretation/reporting of data: Results are reported as within acceptable limits, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
  • Referral to Specialty Care Center: Patients with an abnormal newborn screen for biotinidase deficiency are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of biotinidase deficiency.
Diagnosis

Diagnostic testing includes measuring serum biotinidase enzyme activity. There may also be abnormalities on urine organic acid analysis and plasma acylcarnitine analysis. Molecular genetic testing of the BTD gene is available.

Treatment

Treatment is oral supplementation with biotin.

Prognosis

Prognosis is excellent if biotin treatment is started before the onset of symptoms and taken continuously.

Screened Disorders Type
Definition

Biotinidase deficiency is a disorder of vitamin metabolism (inherited metabolic disorder).

Biotinidase deficiency is caused by mutations in the BTD gene. Biotin is in many foods (milk, egg yolk). The enzyme biotinidase is needed to make additional biotin available for processes in the body, including the break down of other components of food (fat, protein, carbohydrates).