A 3-year-old child presents with pallor, jaundice, and splenomegaly. CBC shows MCV 62 fL, MCHC elevated at 38 g/dL, and osmotic fragility increased. EMA (eosin-5-maleimide) binding test is reduced to 68% of normal. Which protein deficiency most likely underlies this condition?

• A Ankyrin-1 (ANK1 mutation) — most common cause overall in hereditary spherocytosis ✓
• B Alpha-spectrin (SPTA1 mutation) — most common cause of hereditary spherocytosis
• C Band 3 (anion exchanger 1, SLC4A1 mutation) — most common cause in Northern European families
• D Protein 4.2 (EPB42 mutation) — most common cause in Japanese patients

Explanation

Ankyrin-1 mutations (ANK1 gene) account for approximately 40–65% of hereditary spherocytosis cases in Northern European populations, making it the most common cause overall. Band 3 mutations are the second most common (~25%). The EMA binding test detects a reduction in Band 3/Rh complex; it is positive (reduced binding) in most HS subtypes. MCHC elevation reflects dehydration of spherocytes. Protein 4.2 mutations are a specific Japanese HS variant. Alpha-spectrin mutations are the most common recessive form of HS.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.