Initial biotinidase enzyme test to diagnose or rule out BTD
Biotinidase deficiency (BTD), a disorder that affects approximately 1 in 60,000 individuals, is caused by biallelic pathogenic variants in the BTD gene. Specific variants are associated with the degree of deficiency, either partial or profound. Molecular testing of the BTD gene may be useful if enzymatic testing suggests BTD.
Deficiency in biotinidase enzymatic activity impairs the body’s ability to recycle and reuse the vitamin biotin, resulting 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.
- 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)
- Developmental delay
- Vision problems
- Hearing loss
- Partial BTD (10-30% of normal biotinidase activity)
- Newborn screening for BTD is performed across the United States.
- 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.
- 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 by BTD
aThe variant database hosted by ARUP Laboratories is a helpful resource that 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.
National Organization for Rare Disorders (NORD). Rare Disease Database: Biotinidase deficiency. [Published: 2019; Accessed: Feb 2021]
Hayek W, Dumin Y, Tal G, et al. Biotinidase deficiency: a treatable neurological inborn error of metabolism. Isr Med Assoc J. 2019;21(3):219-221.
Strovel ET, Cowan TM, Scott AI, et al. Laboratory diagnosis of biotinidase deficiency, 2017 update: a technical standard and guideline of the American College of Medical Genetics and Genomics. Genet Med. 2017;19(10).
Wolf B. Biotinidase deficiency should be considered in individuals thought to have multiple sclerosis and related disorders. Mult Scler Relat Disord. 2019;28:26-30.
Wolf B. Biotinidase deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews, University of Washington; 1993-2021. [Updated Jun 2016; Accessed: Feb 2021]
American College of Medical Genetics and Genomics. Biotinidase deficiency [algorithm]. [Published: 2006; Accessed: Feb 2021]