Feedback
EIF2AK4-Associated Disorders (EIF2AK4) Sequencing
2010696
Ordering Recommendation

Preferred test to confirm diagnosis or assess carrier status for an EIF2AK4-associated disorder, pulmonary capillary hemangiomatosis (PCH), and pulmonary veno-occlusive disease (PVOD).

Mnemonic
EIF2AK4FGS
Methodology
Polymerase Chain Reaction/Sequencing
Performed
Varies
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.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), 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: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable 
Reference Interval
By report
Interpretive Data
Background Information for EIF2AK4-Associated Disorders (EIF2AK4) Sequencing
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).
Incidence:
Unknown.
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.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Components
Component Test Code*Component Chart NameLOINC
2010697EIF2AK4 Sequencing - Specimen
2010698EIF2AK4 Sequencing - Interpretation
* 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
  • pulmonary arterial hypertension
  • Pulmonary capillary hemangiomatosis
  • pulmonary veno-occlusive disease