Biotinidase Deficiency (BTD) Sequencing

Molecular DNA test to confirm a diagnosis of BTD when biotinidase enzymatic activity is low

Related Tests

Initial biotinidase enzyme test to diagnose or rule out BTD

Useful when a pathogenic familial variant identifiable by sequencing is known

Biallelic pathogenic variants in the BTD gene are the cause of biotinidase deficiency (BTD), a disorder that affects approximately 1 in 60,000 individuals.  Specific variants are associated with the degree of deficiency, partial or profound. Molecular testing of the BTD gene may be useful if enzymatic testing suggests BTD.

The deficiency in biotinidase enzymatic activity impairs the body’s ability to recycle and reuse the vitamin biotin, and results primarily in neurologic and dermatologic manifestations.   Timely diagnosis is important; early identification and treatment of BTD can prevent and even reverse some symptoms, whereas untreated BTD may result in permanent neurologic, visual, and hearing impairment.   Refer to the ARUP Consult Biotinidase Deficiency topic for additional information about screening and laboratory testing for this condition.

Disease Overview


  • Carrier frequency: 1/120 
  • Variants confer 
    • Profound BTD in 1/~137,000
    • Partial BTD in 1/~110,000
    • Profound and partial BTD (combined incidence) in 1/~61,000


  • Profound BTD (<10% of normal biotinidase activity) 
    • Seizures
    • Developmental delay
    • Hypotonia
    • Ataxia
    • Vision problems
    • Hearing loss
    • Alopecia
    • Rashes
  • Partial BTD (10-30% of normal biotinidase activity) 
    • May manifest symptoms associated with profound BTD in times of stress (eg, surgery or infection)


  • Newborn screening for BTD is performed across the United States (3-Strovel, 2017)
  • Confirmatory testing following an abnormal newborn screen includes evaluation of enzyme activity in serum and may include molecular testing of the BTD gene 

Refer to the American College of Medical Genetics and Genomics Biotinidase Deficiency algorithm for more information 





Autosomal recessive


More than 200 different variants have been identified in the BTD gene. 

Test Interpretation


  • Clinical sensitivity: 99%
  • Analytical sensitivity/specificity: 99%


Variant(s) Detecteda

Clinical Significance

2 pathogenic BTD gene variants identified on opposite chromosomes

Predicts a diagnosis of BTD

1 severe and 1 mild BTD gene variant identified

Predicts partial BTD

1 copy of a pathogenic BTD gene variant identified

Predicts that individual is at least a carrier of BTD

No pathogenic gene variants detected by sequencing

Likelihood is reduced that the individual is a carrier of or affected with BTD

aThe variant database hosted by ARUP Laboratories  is a helpful resource and includes information about more than 200 variants that affect biotinidase.


  • Variants of unknown clinical significance may be identified
  • Does not detect:
    • Large deletions or duplications
    • Deep intronic or regulatory region variants
  • Diagnostic errors can occur due to rare sequence variations