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.
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 Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81479

Components
Component Test Code* Component Chart Name LOINC
2010697 EIF2AK4 Sequencing - Specimen
2010698 EIF2AK4 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
EIF2AK4-Associated Disorders (EIF2AK4) Sequencing