With the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1, SPTB, ANK1, SLC4A1, and EPB42. However, mutations in HS-related genes are dispersed and nonspecific in the diagnosis of some HS patients, indicating significant heterogeneity in the molecular deficiency of HS. It is necessary to provide the molecular and genetic characteristics of these 5 genes for clinicians to examine HS. Here, we reviewed the recent proposed molecular genetic mechanisms of HS.

The objective of this study is to compare and evaluate the diagnostic value of hereditary spherocytosis (HS) by three screening tests, comparing mean spherical corpuscular volume (MSCV) to mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and flow cytometric osmotic fragility test. Peripheral blood was collected from 237 participators diagnosed at the First Affiliated Hospital of Guangxi Medical University, including 56 hereditary spherocytosis patients, 86 thalassemia patients, and 95 healthy people. The samples were examined by three tests, and the three screening tests were evaluated by the sensitivity and specificity of tests. The sensitivity was only 41.07%, and specificity was 94.47% when using MCHC >355 g/L as diagnostic criteria. The sensitivity was 89.28%, and specificity was 96.14% when using MSCV < MCV as the optimum cutoff point. When using the residual red cell percentage <23.6% as the diagnostic threshold in flow cytometric osmotic fragility test, the sensitivity was 85.71% and the specificity was 97.24%. Flow cytometry osmotic fragility test or comparing MSCV to MCV combined with smear examination of peripheral red blood cells morphology can be a simple, practical, and accurate hereditary spherocytosis (HS) laboratory screening method.

Measurements of the MCV higher than the MSCV can be considered an ideal index to distinguish rapidly HS from thalassemia.