Hemoglobin G‑Philadelphia is an alpha‑globin chain variant caused by a point substitution at position 68 [α68(E17) Asn→Lys]. The variant is generally clinically silent but can be diagnostically challenging, particularly when present in the homozygous state and when co‑inherited with deletional alpha‑thalassemia such as the -α3.7 deletion. This case report describes an incidental discovery of homozygous Hb G‑Philadelphia identified during routine glycated hemoglobin testing.
The reported patient was a 28‑year‑old woman from southeastern Morocco. She presented with refractory hypochromic microcytic anemia, with laboratory indices reported in the abstract as hemoglobin (Hb) 10.6 g/dL, mean corpuscular volume (MCV) 60.5 fL, and mean corpuscular hemoglobin (MCH) 20.3 pg. A family history of type 2 diabetes mellitus prompted performance of an HbA1c assay.
An HbA1c measurement performed on a Bio‑Rad D‑100 HPLC system revealed an atypical hemoglobin peak eluting in the D window, representing 87.44% of the measured hemoglobin fraction. This unexpected chromatographic profile suggested the presence of a hemoglobin variant interfering with routine HbA1c analysis and warranted further hematologic and molecular evaluation.
Following the abnormal HbA1c HPLC result, the case underwent additional laboratory investigations. The investigators used a second HPLC platform (HPLC Variant II), capillary electrophoresis, and acid pH gel electrophoresis to characterize the hemoglobin abnormality. These complementary techniques confirmed the presence of homozygous Hb G‑Philadelphia in the patient. The abstract does not provide detailed chromatography traces, numeric results from the confirmatory platforms beyond the D‑window proportion on the initial instrument, or exact electrophoretic mobilities.
Molecular analysis verified the hemoglobin variant and demonstrated an association with mild alpha‑thalassemia. The abstract specifies that the alpha‑thalassemia was related to the -α3.7 deletion. No additional molecular sequencing data, zygosity details beyond homozygosity for Hb G‑Philadelphia, or other genetic findings are reported in the abstract.
A targeted family study was reported. The patient’s daughter was found to be a heterozygous carrier of Hb G‑Philadelphia and to carry a cis -α3.7 alpha‑thalassemia trait. The abstract does not report further clinical data, hematologic indices, or follow‑up information for family members beyond their carrier status.
This case illustrates several important points for clinical laboratories and clinicians:
Routine HbA1c assays by HPLC can incidentally detect hemoglobin variants when aberrant peaks or abnormal elution profiles are observed. Such findings should prompt confirmatory testing with orthogonal methods.
Hb G‑Philadelphia, although often clinically silent, may present diagnostic complexity when homozygous and when co‑inherited with deletional alpha‑thalassemia, potentially contributing to microcytic anemia as in this patient.
Use of multiple laboratory modalities—HPLC on different systems, capillary electrophoresis, and acid pH gel electrophoresis—assisted in confirming the variant in this report. Molecular genetic testing established the variant and its association with the common -α3.7 deletion.
Family screening identified a heterozygous carrier state and a cis -α3.7 trait in the daughter, underscoring the hereditary nature of these findings and the relevance of cascade testing when a variant is discovered.
The source for this summary is the PubMed abstract of a case report. The abstract provides limited information and does not include several potentially relevant details, including:
When interpreting this case for clinical practice, readers should be aware that the abstract summarizes core findings but omits full methodological and clinical detail that may be present in the full text of the report.
A 28‑year‑old woman with refractory hypochromic microcytic anemia was found incidentally to have homozygous Hb G‑Philadelphia after an abnormal HbA1c result on HPLC. Confirmatory hemoglobin phenotyping and molecular analysis demonstrated the variant and its association with mild alpha‑thalassemia due to the -α3.7 deletion. Family testing identified the daughter as a heterozygous carrier and cis -α3.7 α‑thalassemia trait. The case highlights the need for further evaluation of unexpected HPLC hemoglobin patterns and the role of combined laboratory and molecular testing to characterize hemoglobin variants. The abstract does not report extended clinical follow‑up, management, or full molecular detail.