Clinical characteristics, genotype-phenotype correlation, and prognostic follow-up of 48 Chinese children with hereditary spherocytosis

Abstract

Objective This retrospective single-center observational study aimed to characterize clinical phenotypes and pathogenic mutation spectra in Chinese children with hereditary spherocytosis (HS), analyze genotype–phenotype correlations. Methods Clinical and genetic data of 48 pediatric HS patients admitted to the First Affiliated Hospital of Naval Medical University from May 2016 to March 2024 were retrospectively analyzed. Clinical indices were compared across subgroups stratified by mutant genes and variant types. Forty patients were followed up via telephone to record post-discharge symptoms, therapies and complications such as cholelithiasis. Results Forty-eight pathogenic variants were confirmed, including 13 novel mutations. SPTB (43.75%) and ANK1 (37.5%) predominated, and 28 patients had positive family histories. Moderate-severe anemia patients presented earlier diagnosis, more transfusions and lower MCHC. ANK1 variants correlated with higher reticulocyte levels and more transfusion dependence; splicing variants were linked to elevated reticulocytes and higher splenomegaly rates, while missense variants yielded milder manifestations. Among 40 followed patients, 12 received splenectomy with resolved hemolysis, no transfusions, improved exercise tolerance and unimpaired growth. No children had a height below P3, and growth profiles were similar between splenectomized and non-splenectomized patients. Conclusion This is the largest Chinese single-center cohort with the longest reported follow-up of pediatric HS, featuring distinct local mutational profiles. This study enriches the Chinese HS mutation spectrum and guides clinical management, genetic counseling and future gene therapy research for pediatric HS.