Q. A 14-year-old boy presents with fatigue, mild jaundice, and splenomegaly. His hemoglobin is 10.5 g/dL, MCV is 82 fL, and MCHC is high 37 g/dL. His father had a similar history of chronic anemia and underwent splenectomy. What is the most likely diagnosis?

Explanation

## Correct Answer: D. Hereditary spherocytosis Hereditary spherocytosis (HS) is the discriminating diagnosis here because of the constellation of **elevated MCHC (37 g/dL)**, **family history of chronic hemolytic anemia with splenectomy**, and **mild jaundice with splenomegaly**. MCHC elevation is pathognomonic for HS—it occurs because spherocytes have a reduced surface-area-to-volume ratio, concentrating hemoglobin within the cell. The father's history of splenectomy is a key clue: splenectomy is the definitive treatment for HS, dramatically improving hemoglobin and reducing transfusion dependence. HS is an autosomal dominant condition (75% of cases) affecting the red cell membrane proteins (spectrin, ankyrin, band 3), causing osmotic fragility and hemolysis in the spleen. The patient's mild anemia (Hb 10.5 g/dL), normocytic indices (MCV 82 fL), and compensatory reticulocytosis (not mentioned but expected) fit the chronic hemolytic pattern. The osmotic fragility test and eosin-5-maleimide (EMA) binding test would confirm diagnosis in Indian practice. Splenectomy is the gold standard treatment in India for symptomatic HS, as seen in the father's case. ## Why the other options are wrong **A. Thalassemia minor** — Thalassemia minor presents with **low or normal MCHC** (hypochromic), **microcytic anemia (MCV <75 fL)**, and **normal or elevated RBC count**. The high MCHC (37 g/dL) rules this out decisively. Thalassemia minor does not cause jaundice or splenomegaly in childhood. Family history would show consanguinity and Mediterranean/Asian ethnicity, not splenectomy for hemolysis. **B. G6PD deficiency** — G6PD deficiency causes **episodic hemolytic crises** triggered by oxidative stress (fava beans, sulfonamides, infections), not chronic hemolysis. Between crises, hemoglobin and indices are normal. MCHC would not be elevated. The father's history of chronic anemia requiring splenectomy does not fit G6PD's acute-crisis pattern. G6PD is X-linked, so inheritance pattern differs from the autosomal dominant presentation here. **C. Autoimmune hemolytic anemia** — AIHA presents with **positive direct Coombs test** (not mentioned), **spherocytes on blood smear**, but **normal or low MCHC**, not elevated. AIHA is typically acquired (secondary to SLE, lymphoma, infections), not inherited. A father with chronic AIHA requiring splenectomy is unusual; AIHA does not run in families as a genetic trait. The clinical presentation lacks the acute hemolytic episodes typical of AIHA. ## High-Yield Facts - **Elevated MCHC (>36 g/dL)** is pathognomonic for hereditary spherocytosis due to reduced surface-area-to-volume ratio of spherocytes. - **Autosomal dominant inheritance** in ~75% of HS cases; father's splenectomy history is a red flag for familial hemolytic anemia. - **Osmotic fragility test** (increased fragility in hypotonic saline) and **EMA binding test** are gold-standard confirmatory tests in Indian labs. - **Splenectomy** is the definitive treatment for symptomatic HS, improving hemoglobin by 1–2 g/dL and reducing transfusion needs. - **Spherocytes on blood smear** (small, dense, hyperchromic RBCs) are the morphologic hallmark; absent in thalassemia or G6PD. - **Chronic hemolysis** with mild jaundice, reticulocytosis, and splenomegaly distinguish HS from acute hemolytic crises of G6PD. ## Mnemonics **HS = High MCHC + Hereditary + Spherocytes** Remember HS by the triad: **H**igh MCHC (only hemolytic anemia with elevated MCHC), **H**ereditary (autosomal dominant), **S**pherocytes (on smear). When you see elevated MCHC in a hemolytic anemia, think HS first. **OSMOTIC FRAGILITY = HS Diagnosis** **O**smotic **F**ragility test is the gold standard for HS. RBCs lyse in hypotonic saline earlier than normal because spherocytes have less surface area to accommodate water influx. Use this when Coombs is negative and MCHC is high. ## NBE Trap NBE pairs elevated MCHC with hemolytic anemia to lure students toward AIHA (which also has spherocytes on smear) or thalassemia (which has family history). The discriminator is that **only HS has elevated MCHC**; AIHA has normal/low MCHC, and thalassemia is hypochromic. The father's splenectomy is the second trap—students may miss that splenectomy is curative for HS but only palliative for other hemolytic anemias.</trap> <parameter name="textbookRef">Robbins & Cotran Pathologic Basis of Disease, Ch. 12 (Red Blood Cell Disorders); Harrison's Principles of Internal Medicine, Ch. 99 (Hemolytic Anemias)</textbookRef> <parameter name="clinicalPearl">In Indian pediatric practice, a child presenting with chronic mild anemia, jaundice, and splenomegaly with a family history of splenectomy should raise immediate suspicion for HS. Unlike thalassemia (common in India), HS is less common but often missed because students focus on MCV rather than MCHC. Splenectomy remains the gold standard in Indian centers for symptomatic HS, offering dramatic improvement in hemoglobin and quality of life.</clinicalPearl> </invoke>