Misdiagnosis of β-Thalassemia Major Due to Chinese ^Gγ+(^Aγδβ)⁰-Thalassemia Combined with β⁰-Thalassemia

Abstract

δβ-thalassemia is a rare type of thalassemia characterized by increased Hb F levels, including mainly Chinese ^Gγ(^Aγδβ)⁰-thalassemia, Yunnanese ^Gγ(^Aγδβ)⁰-thalassemia, Cantonese ^Gγ(^Aγδβ)⁰-thalassemia in China. Due to the low rate of δβ-thalassemia carriers, there are few reports of δβ-thalassemia combined with β-thalassemia causing β-thalassemia major. Herein, we described the combination of Chinese ^Gγ(^Aγδβ)⁰-thalassemia and β-thalassemia leading to β-thalassemia major in a Chinese patient. Hemoglobin analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by gap-polymerase chain reaction (Gap-PCR) and PCR and reverse dot blot (PCR-RDB). Multiple ligation-dependent probe amplification (MLPA) was used to detect the large deletion, and Gap-PCR confirmed the deletion. A CE result showed an elevated Hb F level of 98.7% and 11.7% in the proband and her mother, but the proband was diagnosed with β^CD17M/β^CD17M using routine genetic analysis. However, her father was heterozygous for CD17 in β-globin, and her mother was detected as SEA heterozygous. The further analysis presented that the proband had actually missed the diagnosis of Chinese ^Gγ(^Aγδβ)⁰-thalassemia by MLPA and PCR-RDB. Finally, the genotype of the proband was corrected from β^CD17M/β^CD17M to β^CD17M/β^{Gγ(Aγδβ)0}. This is the first report of Chinese ^Gγ(^Aγδβ)⁰-thalassemia combined with β-thalassemia resulting in β-thalassemia major in China. Screening for δβ-thalassemia by Hb analysis could be an effective method.

Keywords:

• Thalassemiaδβ-thalassemia
• hereditary persistence of fetal hemoglobin (HPFH)
• Hb F

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the Natural Science Foundation of Guangxi [2023GXNSFAA026102] and the Health Department Research Fund of Guangxi [Z20200076].