Hereditary spherocytosis overlooked for 7 years in a pediatric patient with β-thalassemia trait and novel compound heterozygous mutations of SPTA1 gene

Abstract

Objectives: We aimed to determine the clinical and genetic characteristics of a boy diagnosed with the β-thalassemia trait. He also had hereditary spherocytosis (HS) that had been overlooked for 7 years. Methods: Blood samples collected from the proband and his family were assessed by laboratory tests, and next-generation sequencing (NGS) and Sanger sequencing. Results: The β-thalassemia trait was complicated with HS in the proband. Compound heterozygous mutations of the Spectrin Alpha, Erythrocytic 1 (SPTA1) gene, c.83G > A and c.190G > A in the proband were inherited from his mother and father, respectively, and he also had the heterozygous c.126_129delCTTT mutation in the Hemoglobin Subunit Beta (HBB) gene. The c.190G > A mutation has not yet been added to the Human Gene Mutation Database (HGMD®). The heterozygous HBB c.126_129delCTTT mutation was inherited from his mother, and his older brother also had this mutation. Conclusion: Compared with other patients with either HS or β-thalassemia, this proband with both HS and the β-thalassemia trait had very complicated laboratory findings, which resulted in HS being overlooked for 7 years. Genetic testing is invaluable for the differential diagnosis of hereditary anemias with overlapping clinical features.

Novel mechanism of hereditary pyropoikilocytosis phenotype due to co‐inheritance of β globin and α spectrin mutations

“…In this we describe not only a novel HBB mutation leading to autosomal dominant β-thalassemia, but also provide a novel etiology of the HPP phenotype. 10,11…”

“…The inheritance of Hb Santo Domingo and the SPTA1 alleles was traced in family studies (Figure 1(A) and Figure S2), which were limited This study illustrates the diagnostic challenge in a case of coinheritance of defects in the RBC membrane and hemoglobin. A few such rare cases have been described 10,11 where the presence of hereditary spherocytosis or elliptocytosis enhances the severity of β-thalassemia, and also adversely influences the RBC morphology. In this we describe not only a novel HBB mutation leading to autosomal dominant β-thalassemia, but also provide a novel etiology of the HPP phenotype.…”

Peripheral Blood Smear Findings in 2 Patients With Coexisting Thalassemia and Hereditary Spherocytosis

“…Hemolytic anemia is a common finding of thalassemia and hereditary spherocytosis (HS); however, these are 2 distinct clinical entities that have very different presentations. Few reports are available about the coexistence of thalassemia and HS in the same patient 1–5…”

“…6 As osmotic fragility may be normal in both thalassemia and HS, it is not considered a gold standard for the diagnosis of HS. [1][2][3][4][5] As well, Hb electrophoresis may not be demonstrative, especially for α-thalassemia and dominant thalassemia intermedia. We believe that morphologic findings may be helpful for diagnosis in atypical cases with inherited hemolytic anemia.…”

“…The diagnosis of HS is based on either typical clinical and morphologic findings in families with known HS history or positive EMA-binding tests and genetic tests in atypical cases without familial HS 6. As osmotic fragility may be normal in both thalassemia and HS, it is not considered a gold standard for the diagnosis of HS 1–5. As well, Hb electrophoresis may not be demonstrative, especially for α-thalassemia and dominant thalassemia intermedia.…”