Disease-modifying influences of coexistent G6PD-deficiency, Gilbert syndrome and deletional alpha thalassemia in hereditary spherocytosis: A report of three cases

BackgroundHereditary spherocytosis (HS) is a common inherited hemolytic anemia characterized by heterogeneous clinical presentations with variable degrees of anemia, jaundice, splenomegaly and gallstones. Although the underlying genetic defects in red cell membrane proteins may explain many phenotypic variations, a proportion of variability may be due to other co-inherited factors like enzymopathies, thalassemias and Gilbert syndrome. Associations of HS with glucose-6-phosphate dehydrogenase (G6PD) deficiency and Gilbert syndrome in isolation have been reported previously.MethodsWe describe 3 adult cases of HS with concomitant Gilbert syndrome and G6PD-Mediterranean mutations (2 hemizygous males, aged 15 and 35 y and 1 heterozygous 25-y female).ResultsTwo patients required multiple transfusions that required splenectomy for management. One patient (15 y male) also carried the single gene alpha 4.2 deletion and was less symptomatic.ConclusionsThese cases illustrate the importance of clinico-pathological correlation and judicious extended testing for various contributing factors that may modify the clinical course of HS patients. G6PD deficiency is also a common enzymopathy in India and can contribute to the phenotypic heterogeneity. Its recognition is important for advising avoidance of oxidizing drug exposure.