Confirm a suspected diagnosis of hereditary paraganglioma-pheochromocytoma when SDHB, SDHC, and SDHD gene testing is negative.
- Patient Preparation
- Lavender (EDTA), pink (K2 EDTA), or Yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndrome is characterized by paragangliomas (neuroendocrine tumors of the autonomic nervous system) and pheochromocytomas (paragangliomas of the adrenal medulla). Pathogenic germline mutations in a number of genes, including SDHA, predispose to paraganglioma and pheochromocytoma with risk of malignant transformation.
Incidence: About 1 in 300,000 per year.
Inheritance: Autosomal dominant.
Cause: Pathogenic succinate dehydrogenase, subunits A, B, C, and D (SDHA, SDHB, SDHC, and SDHD) gene mutations. Mutations in other genes, including TMEM127, EGLN1, MAX, and SDHAF2, may also be causative.
Clinical Sensitivity: Less than 3 percent.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the SDHA gene. Sequencing primers are specifically selected to target the functional SDHA gene.
Analytical Sensitivity and Specificity: 96 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletions/duplications in SDHA are not detected. In some cases, results may be uninterpretable due to technical limitations in the presence of pseudogenes.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
|Component Test Code*||Component Chart Name||LOINC|
|2011462||Hereditary PGL/PCC (SDHA) Seq - Spcmn||31208-2|
|2011464||Hereditary PGL/PCC (SDHA) Seq - Interp||35474-6|
- subunit A flavoprotein
- succinate dehydrogenase complex