Clinicohematological and Genetic Profile of Hereditary Spherocytosis in Children: An Experience From a North Indian Center.

BACKGROUND

Hereditary spherocytosis (HS) is a genetically and clinically diverse red cell membrane disorder, with limited clinical and molecular data on pediatric patients from India.

METHODS

This ambispective study, conducted at a North Indian tertiary center over a period of 6 years, evaluated HS patients for clinical, laboratory, genetic, and treatment outcomes.

RESULTS

Forty-seven patients (33 males, 14 females; mean age 12.1±8.7 yrs) were analyzed. Family history was contributory in 40.4%. Around 72.3% patients required at least one PRBC transfusion by the time of analysis, while 9 were transfusion dependent. Hemolytic facies and growth retardation were seen in 25.6% and 30.7%, while gallstones were found in 42.5%. MCHC was 32.2±1.92% and was not found to be a useful screening test. Incubated osmotic fragility testing (iOFT) was positive in 36 cases (sensitivity 76.6%), while eosin-5-maleimide (EMA) binding by flow cytometry was positive in 41 cases (sensitivity 87.2%), detecting all cases missed or equivocal on iOFT and demonstrating superior diagnostic yield. The remaining 6 cases were confirmed by genetic testing, which served as the definitive diagnostic modality. Among 34 patients tested genetically, mutations were found in ANK1 (n=14), SPTB (n=12), SLC4A1 (n=3), EPB42 (n=4), and SPTA1 (n=1). Beyond classic HS mutations, additional findings included PKLR mutations (n=2), hereditary elliptocytosis (n=2), dehydrated stomatocytosis (n=2), and Gilbert syndrome (n=4) with cholelithiasis. Genetic testing refined diagnoses, reclassifying one Congenital Dyserythropoietic Anemia (CDA) case as HS and 4 HS cases as alternative etiologies.

CONCLUSION

This study underscores the clinical and genetic heterogeneity of Indian HS, demonstrating the value of combining the EMA dye test with genetic sequencing. The disease impacted facial features and growth, while splenectomy showed good outcomes in severe cases.