A 3-year-old boy presents with severe hypoglycemia, hepatomegaly, and lactic acidosis after a 4-hour fast. Enzyme assay shows deficiency of phosphofructokinase (PFK). His 6-year-old sister has a similar presentation but with normal lactate levels and prominent muscle pain on exertion. Which feature best distinguishes PFK deficiency from pyruvate kinase (PK) deficiency?

Explanation

## Distinguishing PFK Deficiency from PK Deficiency ### Pathophysiology Overview **Key Point:** PFK deficiency (glycolysis block proximal to pyruvate formation) and PK deficiency (glycolysis block at final step) cause different metabolic consequences and clinical phenotypes. ### Comparison Table | Feature | PFK Deficiency | PK Deficiency | |---------|---|---| | **Glycolytic block** | Early (glucose-6-phosphate accumulation) | Late (pyruvate formation impaired) | | **Lactate production** | ↓ (less pyruvate formed) | ↑↑ (pyruvate shunted to lactate) | | **Muscle involvement** | **Prominent** — myalgia, cramps, exercise intolerance | Minimal — mainly hemolytic anemia | | **RBC hemolysis** | Mild or absent | **Severe** — chronic hemolytic anemia | | **Hepatomegaly** | Present (glycogen storage) | Present (glycogen storage) | | **Lactic acidosis** | Absent or mild | **Marked** | ### Clinical Pearl **High-Yield:** PFK deficiency is **muscle-predominant** (Type VII glycogenosis); PK deficiency is **RBC-predominant**. This distinction is the single best discriminator: - **PFK deficiency** → **Myalgia, exercise intolerance, muscle cramps** are hallmark features; patients avoid exertion; lactate is *normal or low* because pyruvate formation is blocked upstream. - **PK deficiency** → **Hemolytic anemia, jaundice, splenomegaly** dominate; lactate is *markedly elevated* because pyruvate accumulates and shunts to lactate; muscles are spared. ### Why Each Option Fails or Succeeds - **Option 1 (Elevated lactate):** This is a feature of PK deficiency, not PFK deficiency. In PFK deficiency, lactate is *low* because the glycolytic block prevents pyruvate formation. This is a trap for students who confuse "enzyme deficiency" with "lactate elevation." - **Option 2 (Muscle symptoms):** ✓ **CORRECT.** Myalgia and exercise intolerance are the defining clinical feature of PFK deficiency and are *absent* in PK deficiency. This is the best discriminator. - **Option 3 (Hepatomegaly and growth retardation):** Both conditions present with hepatomegaly and growth retardation due to glycogen accumulation. Not discriminatory. - **Option 4 (Hemolytic anemia with spherocytes):** This is characteristic of PK deficiency (RBCs depend entirely on glycolysis for ATP). PFK deficiency does not cause significant hemolysis. ### Mnemonic **"PFK = Muscle, PK = RBC"** - **PFK** → **P**roximal block → **F**atigue/muscle pain - **PK** → **P**yruvate **K**inase → **K**ills RBCs (hemolysis) [cite:Robbins 10e Ch 7; KD Tripathi 8e Ch 12]