Hereditary Hemolytic Spherocytosis in the Active-Duty Population: A Unique Case

Hereditary spherocytosis (HS) is a common inherited cause of hemolytic anemia and is most often diagnosed in childhood. While the condition does not by itself disqualify affected adults from military service, its autosomal dominant inheritance has important implications for offspring, who may develop more severe disease. We report the case of a 38-year-old active-duty US Army soldier of Saipanese (Chamorro) descent who presented with persistent, unexplained fatigue -- most pronounced during strenuous physical activity -- despite adequate sleep. He had no formal family history of anemia, although one of his three children carries an undiagnosed anemia. Physical examination revealed splenomegaly. Laboratory evaluation demonstrated compensated hemolysis, as evidenced by a low-normal hemoglobin maintained by a reticulocyte response of 9.36%, a normal mean corpuscular volume, an elevated mean corpuscular hemoglobin concentration of 36.7 g/dL -- a characteristic diagnostic feature of HS -- an elevated red cell distribution width, undetectable haptoglobin, and elevated lactate dehydrogenase and indirect bilirubin. The peripheral blood smear was reported by the staff pathologist as a normocytic, normochromic anemia with occasional spherocyte-like forms and mild polychromasia. The patient also demonstrated mild-to-moderate hepatic iron overload despite the absence of transfusions. Genetic testing identified a heterozygous nonsense mutation in the SPTB gene, c.2175G>A (p.Trp725Ter), introducing a premature termination codon within exon 12 and consistent with HS type II. A concurrent pyruvate kinase variant of uncertain significance was also identified. The variant identified in our patient was subsequently deposited in ClinVar by the clinical testing laboratory (Variation ID: 2428713; classified pathogenic) and is absent from gnomAD v4.1.1; to our knowledge, this variant has not previously been described in the published clinical literature. This report provides the clinical and phenotypic characterization of the patient whose testing contributed to that ClinVar submission, and highlights the value of genetic evaluation in adults with unexplained hemolysis, particularly when the offspring is also affected.