# Diagnosis of hemogobinopathies in the clinical laboratory: an occult Hofu hemoglobin on HPLC

## TL;DR

This paper discusses a case where a rare hemoglobin variant, Hofu, was misdiagnosed due to its similarity to another hemoglobin type using standard lab tests.

## Contribution

The paper highlights the diagnostic challenges of Hofu hemoglobin due to its near-identical HPLC retention time with HbA(0).

## Key findings

- Hb Hofu can be masked by HbA(0) during HPLC analysis, leading to potential misdiagnosis.
- Genetic testing confirmed a mutation in the HBB gene causing Hofu hemoglobin disease.
- Hb Hofu is slightly unstable and may cause anemia in carriers with other disorders.

## Abstract

Hemoglobinopathies are disorders affecting the structure, function and/or production of hemoglobin. These conditions are caused by mutations in the genes encoding globin synthesis. The highly variable clinical manifestations of hemoglobin disorders range from asymptomatic forms to severe anemia. Laboratory tests are crucial for diagnosis.

We report the case of a patient who presented with asthenia. Since the patient had a family history of hemoglobonipathies, screening for erythropathies was performed. High-resolution liquid chromatography (HPLC) showed a normal distribution of hemoglobin levels. In contrast, capillary zone electrophoresis at alkaline pH demonstrated an unidentified rapid migration peak. Genetic testing revealed a mutation in the HBB gene causing Hofu hemoglobin disease.

The hemoglobin variant Hofu is slightly unstable. While heterozygous carriers most frequently remain asymptomatic, they may develop anemia in the presence of other concomitant disorders. Distinctively, the retention time of Hb Hofu on HPLC is very close to that of HbA (0) and they often elute together. Therefore, Hb Hofu may remain masked, thereby leading to the misinterpretation of test results.