Card kit

Invitae Biotinidase Deficiency Test

Test code: 06194

Test description

The Invitae Biotinidase Deficiency Test analyzes the gene BTD, which is associated with biotinidase deficiency. This test is useful for the diagnosis of patients in whom biotinidase deficiency is suspected due to clinical symptoms, abnormal newborn screening results, or biochemical findings.

Disorders tested

Ordering information

Turnaround time:

10–21 calendar days (14 days on average)

New York approved:

Yes

Preferred specimen:

3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)

Alternate specimens:

Saliva, buccal swab, and gDNA are also accepted.
Learn more about specimen requirementsRequest a specimen collection kit

Clinical description and sensitivity

Clinical description:

Profound biotinidase deficiency is generally seen in patients with less than 10% of residual biotinidase activity. Untreated patients with profound biotinidase deficiency can have hypotonia, seizures, alopecia, eczema, metabolic acidosis, and developmental delay. Over time, untreated patients may develop sensorineural hearing loss, candidiasis, ataxia, conjunctivitis, and visual problems such as optic atrophy. Early treatment with pharmacologic doses of biotin is important to prevent irreversible neurologic damage. With early intervention and treatment, patients generally remain asymptomatic.

Partial biotinidase deficiency is the most common clinical subtype of biotinidase deficiency. Many patients with partial biotinidase deficiency have been picked up on newborn screening and remain asymptomatic. Those with symptoms, however, may have intermittent hypotonia, skin rashes, or alopecia during times of prolonged intercurrent illness. Partial biotinidase deficiency is generally seen in patients with 10%–30% of residual biotinidase activity.

Biotinidase deficiency is an enzyme deficiency that affects the recycling of the coenzyme biotin, a water-soluble B vitamin. If untreated, this disorder can result in deficiencies of the four biotin-dependent carboxylases: acetyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase, and pyruvate carboxylase. A biochemical feature of biotinidase deficiency is the abnormal elevation of urine organic acids, including 3-hydroxyisovaleric acid, lactic acid, 3-hydroxypropionic acid, methylcitric acid, 3-methylcrotonylglycine, propionylglycine, and tiglylglycine. Propionylcarnitine (C3) and 3-hydroxyisovalerylcarnitine (C5-OH) can also be elevated. Serum biotinidase activity will be low. Currently, most patients with biotinidase deficiency are identified through newborn screening.

Clinical description and sensitivity

Assay information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Assay information

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Primary panel

1 gene selected
BTD

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