Biotinidase Deficiency (BTD) Sequencing

Casandra

Casandra Test Code AR51311Version 1 (DRAFT)

Performing Lab

Lab ARUP LaboratoriesLab Test ID 3004424CPT Code 81404

Biotinidase Deficiency (BTD) Sequencing

Also known as: BTD NGS

Clinical Use

Order Test

Use

Biotinidase Deficiency (BTD) Sequencing is used to confirm a diagnosis of biotinidase deficiency, which impairs the body's ability to recycle and reuse the vitamin biotin, resulting in neurologic and dermatologic symptoms. Profound BTD manifests with symptoms including ataxia, hypotonia, developmental delay, seizures, vision and hearing problems, alopecia, metabolic acidosis, organic aciduria, and hyperammonemia. Pathogenic germline variants in the BTD gene cause BTD, and the condition is inherited in an autosomal recessive manner. The clinical sensitivity of the test is approximately 99 percent in detecting BTD.

Special Instructions

Informed consent for genetic testing is required for patients in New York. It is important to consider familial genetic testing if there is a known familial pathogenic variant in an affected member. Parental testing can confirm the chromosomal origin of identified pathogenic variants in the patient.

Limitations

This test does not exclude a diagnosis of BTD if negative, as only variants within coding regions and intron-exon junctions are detected. It may miss deletions, duplications, insertions of any size, and deep intronic or regulatory region variants. Technical limitations can affect the detection due to pseudogenes, repetitive, or homologous regions. This test is not for detecting low-level mosaic or somatic variants, gene conversions, complex inversions, translocations, mtDNA mutations, or repeat expansions. Interpretation may be affected by previous allogeneic stem cell transplants, and non-coding transcripts are not analyzed.

Test Details

Methodology

NGS (Targeted)

Biomarkers

This component involves probe hybridization-based capture of all coding exons and exon-intron junctions of the BTD gene, followed by massively parallel sequencing. Sanger sequencing is used to fill in low coverage regions.

BTD

Gene

SNV/Indel • Mutation • Categorical (e.g., Positive / Negative / Indeterminate)