Ordering Recommendation

Use to assess for gamma globin gene variants resulting in neonatal hemolytic anemia, cyanosis or methemoglobinemia in symptomatic infants when other etiologies have been excluded. Use to assess for nondeletional hereditary persistence of fetal hemoglobin (HPFH) in individuals with elevated fetal hemoglobin. Characterizes abnormal hemoglobins identified by electrophoresis suspected to represent gamma chain variants.

Mnemonic
HBG FGS
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Varies

Reported

Within 2 weeks

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

By report

Interpretive Data

Background information for Gamma Globin (HBG1 and HBG2) Sequencing:
Characteristics:
Variants in the gamma globin genes, HBG1 and HBG2, may occasionally result in either a quantitative defect (gamma thalassemia or nondeletional hereditary persistence of fetal hemoglobin) or a qualitative abnormality (gamma variant). Gamma variants resulting in unstable, high- and low-oxygen affinity or M hemoglobin variants may result in hemolytic anemia/hyperbilirubinemia, erythrocytosis/cyanosis, or methemoglobinemia in neonates, respectively. Clinical symptoms related to gamma globin variants commonly resolve after the first six months of life given the switch from fetal hemoglobin expression to adult hemoglobin expression.
Incidence:
Unknown.
Inheritance:
Autosomal dominant.
Cause:
Pathogenic germline variants in HBG1 or HBG2.
Clinical Sensitivity: Unknown. Gamma globin variants are a rare cause of neonatal hemolytic anemia, cyanosis, erythrocytosis, or methemoglobinemia.
Methodology:
Long range PCR followed by nested PCR and bidirectional sequencing of all coding regions, intron-exon boundaries, and 5' proximal promoters of the HBG1 and HBG2 genes.
Analytical Sensitivity and Specificity:
99 percent.
Limitations:
Diagnostic errors can occur due to rare sequence variations or repeat element insertions. Large deletions/duplications, distal regulatory region variants, deep intronic variants, and hybrid gene events 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
3002038 Specimen HBG FGS 31208-2
3002039 HBG FGS Interpretation 53037-8
* 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
Gamma Globin (HBG1 and HBG2) Sequencing