A male neonate develops progressive hemolytic anemia with red cell inclusions (Heinz bodies) and cyanosis unresponsive to methylene blue. NADPH levels in red cells are markedly reduced. Newborn screening for which enzyme deficiency should be prioritized?
- A Glutathione reductase
- B Pyruvate kinase
- C Glucose-6-phosphate dehydrogenase ✓
- D Lactate dehydrogenase
Correct answer: C. Glucose-6-phosphate dehydrogenase
Explanation
Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the HMP shunt; it generates NADPH, essential for maintaining glutathione in its reduced form. G6PD deficiency depletes NADPH, allowing oxidative damage of hemoglobin (Heinz bodies) and RBC membrane. Methylene blue restores methemoglobin only via NADPH-dependent methemoglobin reductase, so it is ineffective when NADPH is absent. Pyruvate kinase deficiency causes hemolysis but not Heinz bodies or cyanosis, and glutathione reductase deficiency is far less common.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.