From the Guidelines
The patient's development of gout is most likely due to an increase in the levels of Ribose 5-P. This is because the symptoms presented, such as fasting hypoglycemia, lactic acidosis, hepatomegaly, and impaired glucagon response, are suggestive of a disorder of glycogen metabolism. According to the study 1, glycogen storage disease type I (GSD I) is characterized by elevated uric acid and lactate concentrations, which are typically associated with the development of gout. The metabolic defect in GSD I leads to shunting of glucose-6-phosphate into the pentose phosphate pathway, producing excess ribose 5-phosphate. This metabolite is subsequently converted to phosphoribosyl pyrophosphate (PRPP), which serves as a substrate for purine synthesis, resulting in elevated uric acid levels and gout.
Key features of the patient's condition include:
- Fasting hypoglycemia and lactic acidosis
- Hepatomegaly
- Impaired glucagon response
- Development of gout
The study 1 highlights the importance of distinguishing between different types of glycogen storage diseases, including GSD I and GSD III, based on clinical and laboratory features. However, the development of gout in the context of these disorders is most closely associated with the accumulation of ribose 5-phosphate, as seen in GSD I.
The other options, such as ATP, dTTP, NADH, and glutamine, are not directly implicated in the development of gout in the context of glycogen storage diseases, as described in the study 1. Therefore, Ribose 5-P is the most likely metabolite responsible for the patient's development of gout.
From the Research
Metabolic Disorders and Gout
- The patient's condition, characterized by fasting hypoglycemia, lactic acidosis, hepatomegaly, and impaired glucagon response, suggests a metabolic disorder affecting glucose and purine metabolism.
- Gout is associated with increased production of purines, which can be linked to abnormalities in the pentose phosphate pathway 2.
- The pentose phosphate pathway is involved in the generation of ribose-5-phosphate, a precursor for purine synthesis.
Purine Synthesis and Gout
- Studies have shown that increased concentrations of ribose-5-phosphate can lead to increased purine synthesis and hyperuricemia 3, 4.
- Elevated intracellular ribose-5-phosphate concentrations can increase the rate of de novo purine biosynthesis by activating the enzyme phosphoribosyl amidotransferase 4.
- Therefore, the patient's development of gout is likely due to an increase in the levels of ribose-5-phosphate, which promotes purine synthesis and uric acid production.