Objective: Hereditary spherocytosis (HS) is a hemolytic anemia with variably severity, caused by defects in the components of red cell membranes. It is characterized by anemia, jaundice, splenomegaly and cholelithiasis. The clinical manifestations vary widely, ranging from nearly asymptomatic to transfusion-dependent or severe life-threatening anemia. It is difficult to identify atypical cases with classical approaches. The known HS gene mutations are SPTA1 gene, SPTB gene, ANK1 gene, SLC4A1 gene and EPB42 gene. In this report, the next-generation sequencing (NGS) was used to analyze our patients with HS and we identified mutations responsible for HS.
Methodology: Patients who were diagnosed with hereditary spherocytosis with osmotic fragility testing between 2007–2019; ten were further tested for molecular background. Diagnosed in our center were analyzed retrospectively. Either NGS or ANK1 Sanger testing were used.
Results: The 10 cases of HS comprised 8 males and 2 females. The age of patients ranged from 5 months to 17 years. Hemolytic anemia, jaundice and splenomegaly were the most common findings in our cases. Gallstones were detected in four patients (40%). The family history was positive in 5 (50%) patients. Splenectomy and cholecystectomy was performed in two cases and three cases, respectively. The results corfirmed ANK1 gene mutation in 50%; SPTB gene mutation in 20%, EBP42 gene mutation in 10%; SPTA1 gene mutation in 10%. The clinical features of the patients are summarized in the Table 1. Table 1. Patient Age Sex Age of diagnosis Family history Splenomegaly Gallstone Splenectomy/Cholecystectomy Mutated gene 1 1 Female 1 year Yes + − −/− SPTB 2 10 Female 10 years Yes + − +/− ANK1 3 12 Female 7 years Yes + + +/+ ANK1 4 12 Female 2 years Yes − + −/+ ANK1 5 10 Male 6 years No − + −/− ABCG8 6 2 Female 5 months No + − −/− ANK1 7 13 Female 15 years Yes + − −/− ANK1 8 8 Female 7 years No + + −/+ EBP42 9 2.5 Male 2 years No + − −/− SPTB 10 19 Female 17 years No + − −/− SPTA1.
Conclusion: Consistent with the literature, the most common gene mutated was ANK1. Collectively, our results suggest that mutation analyses will complement other conventional tests for accurate diagnosis of HS, especially in those who are under transfusion programme and are followed with a diagnosis of unspecified hemolytic anemia.
