Interpretive Handbook

Test 89013 :
Biotinidase Deficiency, BTD Gene, Known Mutation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Biotinidase deficiency is an inherited metabolic disease caused by reduced levels of biotinidase, an enzyme that recycles biotin by releasing it from its metabolic product, biocytin, or exogenous dietary proteins. Biotin is a vitamin that serves as a coenzyme for 4 carboxylases that are essential for amino acid catabolism, gluconeogenesis, and fatty acid synthesis. Depletion of free biotin reduces carboxylase activity, resulting in secondary carboxylase deficiency. Depending on the amount of residual biotinidase activity, individuals can have either profound or partial biotinidase deficiency. Age of onset and clinical phenotype vary among individuals. Profound biotinidase deficiency occurs in approximately 1 in 137,000 live births and partial biotinidase deficiency occurs in approximately 1 in 110,000 live births, resulting in a combined incidence of about 1 in 61,000.


Untreated profound biotinidase deficiency (<10% of normal biotinidase activity) manifests within the first decade of life as seizures, hypotonia, neurosensory hearing loss, respiratory problems, and cutaneous symptoms including skin rash, alopecia, and recurrent viral or fungal infections. Among children and adolescents with profound biotinidase deficiency, clinical features include ataxia, sensorineural hearing loss, developmental delay, and eye problems such as optic neuropathy leading to blindness. Partial biotinidase deficiency (10%-30% of normal biotinidase activity) is associated with a milder clinical presentation which may include cutaneous symptoms without neurologic involvement.


Treatment with biotin has been successful in both preventing and reversing the clinical features associated with biotinidase deficiency. As a result, biotinidase deficiency is included in most newborn screening programs in order to prevent disease. Biotinidase deficiency exhibits a similar clinical presentation to carboxylase and holocarboxylase synthetase deficiency. Therefore, measurement of the biotinidase enzyme is required to differentiate between these diseases and ensure proper diagnosis. Newborn screening for biotinidase deficiency involves direct analysis of the biotinidase enzyme from blood spots obtained shortly after birth. This enables early identification of potentially affected individuals and quick follow-up with confirmatory biochemical and molecular testing.


Biotinidase deficiency is inherited in an autosomal recessive manner, caused by mutations in the biotinidase gene (BTD). The carrier frequency for biotinidase deficiency in the general population is about 1 in 120. Several common mutations in the BTD gene have been identified, accounting for about 60% of affected individuals. Sequencing of the entire BTD gene detects other, less common, disease-causing mutations, increasing the overall detection rate by molecular testing in individuals with confirmed or suspected biotinidase deficiency. While genotype-phenotype correlations are not well established, it appears that certain mutations are associated with profound biotinidase deficiency while others are associated with partial biotinidase deficiency.


Site-specific testing for mutations that have already been identified in an affected patient is useful for confirming a suspected diagnosis in a family member. It is also useful for determining whether at-risk individuals are carriers of the disease and, subsequently, at risk for having a child with biotinidase deficiency.

Useful For Suggests clinical disorders or settings where the test may be helpful

Carrier testing of individuals with a family history of biotinidase deficiency


Diagnostic confirmation of biotinidase deficiency when familial mutations have been previously identified


Prenatal testing when 2 familial mutations have been previously identified in an affected family member

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order BTDMS / Biotinidase Deficiency, BTD Full Gene Analysis.


Analysis is performed for the familial mutation provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with metabolic disease.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Kaye CI, Committee on Genetics: Newborn screening fact sheets. Pediatrics 2006 Sep;118(3):e934-e963

2. Moslinger D, Muhl A, Suormala T, et al: Molecular characterization and neuropsychological outcome of 21 patients with profound biotinidase deficiency detected by newborn screening and family studies. Eur J Pediatr 2003 Dec;162 Suppl 1:S46-49 Epub 2003 Nov 20

3. Nyhan WL, Barshop B, Ozand PT: Multiple carboxylase deficiency/biotinidase deficiency. In Atlas of Metabolic Diseases. Second edition. New York, Oxford University Press, 2005, pp 42-48

4. Wolf B, Jensen KP, Barshop B, et al: Biotinidase deficiency: novel mutations and their biochemical and clinical correlates. Hum Mutat 2005 Apr;25(4):413