Ordering Recommendation

Confirm a suspected diagnosis of hereditary paraganglioma-pheochromocytoma when SDHB, SDHC, and SDHD gene testing is negative.

Mnemonic
SDHA FGS
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Sun- Sat

Reported

14-21 days

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months

Reference Interval
Interpretive Data

Background Information for Hereditary Paraganglioma-Pheochromocytoma (SDHA)Sequencing:
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. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
N/A
CPT Codes

81406

Components
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
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • PGL/PCC
  • subunit A flavoprotein
  • succinate dehydrogenase complex
Hereditary Paraganglioma-Pheochromocytoma (SDHA) Sequencing