Confusable diagnoses · PANCE / PANRE

G6PD Deficiency vs Hereditary Spherocytosis

G6PD Deficiency and Hereditary Spherocytosis are easy to mix up on the boards. Here's a side-by-side comparison — presentation, workup, imaging, and first-line treatment — drawn from our full outlines.

G6PD Deficiency vs Hereditary Spherocytosis at a glance

  • G6PD Deficiency: X-linked enzyme deficiency causing episodic oxidative hemolysis in response to drugs, infection, or fava beans.
  • Hereditary Spherocytosis: Inherited red cell membrane defect producing spherocytes, hemolysis, splenomegaly, and jaundice.
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Side-by-side comparison

FeatureG6PD DeficiencyHereditary Spherocytosis
At a glanceX-linked enzyme deficiency causing episodic oxidative hemolysis in response to drugs, infection, or fava beans.Inherited red cell membrane defect producing spherocytes, hemolysis, splenomegaly, and jaundice.
Classic presentationDark urine and jaundice 1-3 days after starting TMP-SMX (or dapsone, or fava bean ingestion) in a young man of African or Mediterranean descent.; Acute…Triad of hemolytic anemia, jaundice, and splenomegaly with spherocytes on peripheral smear and a negative Coombs test.; Neonatal jaundice often requiring…
Workup / key labsLow quantitative G6PD enzyme activity in a stable patient (away from acute hemolytic episode). Newborn screening available in many states.; CBC — normocytic…Hemolytic anemia + spherocytes + negative DAT + family history OR positive EMA binding test. Genetic testing reserved for atypical/severe or recessive cases.;…
ImagingNot routinely indicatedAbdominal ultrasound — splenomegaly; screen for cholelithiasis in adolescents and adults
First-line treatmentAcute hemolysis: identify and remove offending agent immediately; Supportive care — IV fluids to maintain renal perfusion and clear hemoglobinuria;…Folic acid supplementation (1 mg daily) in moderate-to-severe disease to support compensatory erythropoiesis; Transfusion support for severe anemia or…

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Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.