Recoverable, Record-High Lactic Acidosis in a Patient with Glycogen Storage Disease Type 1: A Mixed Type A and Type B Lactate Disorder

Figure 2

Suggested scheme of altered metabolic pathways and physiologic changes in the case report, leading to extreme hyperlactemia. The inherent disorder, nonfunctioning G6Pase, blocks conversion of G6P to glucose (1). In the absence of continuous glucose supplementation, ensuing hypoglycemia (2) activates stress hormones (catecholamines, glucocorticoids, and glucagon) and suppresses insulin secretion (3). Consequently, glycogenolysis and gluconeogenesis are enhanced, with accelerated generation of glucose-6P (4), which, unable to convert to glucose, undergoes glycolysis with the generation of pyruvate (5). Since PDC is inhibited by PDH kinase, induced by cytokines such as TNF and by depressed insulin, shunting pyruvate to the Krebs cycle is inhibited (6). Excess pyruvate is converted to lactate, especially in the presence of acidosis and with increased G6P (7). A type A component of lactic acidosis results from circulatory failure and tissue hypoperfusion and hypoxia, further intensifying lactate generation (8), and stimulating the release of stress hormones (9). Finally, urinary clearance of excess lactate is hampered due to evolving kidney failure (10). Exogenous catecholamines for circulatory failure (11) may reduce type A lactate generation by the restoration of tissue perfusion in some organs but might intensify type B lactic acidosis via enhanced gluconeogenesis. Scattered lines represent reciprocal association. LDH: lactate dehydrogenase; G6P: glucose-6-phosphate; G6Pase: glucose-6-phosphatase; PDC: pyruvate dehydrogenase complex; PDH: pyruvate dehydrogenase; AKI: acute kidney injury.