Preferred test to confirm diagnosis or assess carrier status for an EIF2AK4-associated disorder, pulmonary capillary hemangiomatosis (PCH), and pulmonary veno-occlusive disease (PVOD).
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), 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: Two main histological patterns of disease have been associated with EIF2AK4 germline mutations: pulmonary capillary hemangiomatosis (PCH) and pulmonary veno-occlusive disease (PVOD). PCH develops from uncontrolled proliferation of capillaries in the pulmonary interstitium. Capillary invasion may impact the pulmonary veins or arteries, alveolar walls and alveolar space, intralobular fibrous septa and bronchi, pericardium, pleura, and mediastinal lymph nodes. PVOD results from occlusion or narrowing of pulmonary veins and venules by fibrous tissue. Clinical presentations vary depending on the affected lung structures and may mimic other forms of pulmonary arterial hypertension (PAH).
Inheritance: Autosomal recessive.
Cause: Pathogenic EIF2AK4 gene mutations.
Clinical Sensitivity: 90 percent for heritable EIF2AK4-associated disorders; less than 10 percent for PAH.
Methodology: PCR followed by bidirectional sequencing of the entire EIF2AK4 coding region and intron-exon boundaries.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletions/duplications will not be detected.
|Component Test Code*||Component Chart Name||LOINC|
|2010697||EIF2AK4 Sequencing - Specimen|
|2010698||EIF2AK4 Sequencing - Interpretation|
- pulmonary arterial hypertension
- Pulmonary capillary hemangiomatosis
- pulmonary veno-occlusive disease