Are both hemolysis and impaired myocyte integrity associated with glucose-6-phosphate dehydrogenase deficiency?

Glucose-6-phosphate dehydrogenase (G6PD) is a potent antioxidant enzyme. G6PD deficiency, predominant among males, is a neonatal "neurotoxic" risk, characterized by episodic hemolysis that is sometimes infection triggered. Clinical risk among heterozygous G6PD-deficient females is often under-recognized. Recent reports of rhabdomyolysis among G6PD-deficient individuals are reviewed here. In one case, a male athlete with G6PD deficiency (<10% activity) experienced multiple, acute episodes of rhabdomyolysis, painful muscle symptomatology, injury and hemolysis after strenuous exertion. Both his mother with G6PD-deficiency (<45% activity) and maternal grandmother have chronic histories of episodic or triggered fatigue-related disruptive symptoms. Other case reports of G6PD-deficient individuals with muscle injury and exertional symptoms (with or without hemolysis) showed unique laboratory

Findings: of elevated creatine kinase, myoglobin, lactate dehydrogenase, creatinine, and aminotransferases levels and myoglobinuria. Disrupted myocyte energetics and loss of cellular integrity can be attributed to impaired downstream pentose phosphate pathway (PPP)-related oxidant stress protection, which is a key enzymatic consequence of G6PD-deficiency. These triggered stresses may explain the muscle fatigue and propensity to exertional injury. Correlation between stress-sensitive-impaired muscle injury among all G6PD-deficient individuals, including neonates, requires further clinical validation to ascertain oxidant-stress impact of impaired PPP-dependent cellular energetics of red blood, white blood, neural, and muscle cells.