Is glycogen storage disease (GSD) associated with lactic acidosis?

Glycogen Storage Disease and Lactic Acidosis

Yes, glycogen storage disease (GSD), particularly type I (von Gierke's disease), is characterized by lactic acidosis as one of its primary metabolic abnormalities. 1

Pathophysiology and Laboratory Findings in GSD Type I

• Initial laboratory findings consistent with GSD I include hypoglycemia, lactic acidosis, hyperuricemia, hypercholesterolemia, and hypertriglyceridemia 1
• The lactic acidosis in GSD I results from impaired glucose-6-phosphatase activity, preventing proper glycogen breakdown and leading to accumulation of lactate 1
• Prior to modern management techniques, GSD type Ia was marked by life-threatening hypoglycemia and lactic acidosis 2
• A glucagon stimulation test in GSD I patients can worsen metabolic acidosis and is not recommended for diagnosis due to risk of acute decompensation 1
• When glucagon stimulation is performed in GSD I, there is a significant increase in blood lactate but little or no increase in blood glucose concentration 1

Differential Diagnosis Among GSD Types

• GSD type I (von Gierke's disease) consistently presents with lactic acidosis 1, 3
• GSD type III (debrancher enzyme deficiency) shows absence of hyperlactatemia and has normal blood lactate and uric acid levels 1
• GSD types VI (hepatic phosphorylase deficiency) and IX (phosphorylase kinase deficiency) typically have normal blood lactate levels, though postprandial elevations can occur 1
• GSD type 0 (glycogen synthase deficiency) presents with postprandial hyperlactatemia rather than fasting lactic acidosis 1

Clinical Implications and Management

• Lactic acidosis in GSD I requires careful monitoring, especially during surgical procedures where it may worsen 4
• During anesthesia management of GSD patients, intraoperative lactic acidosis can develop but typically resolves within 24 postoperative hours 4
• Optimization of metabolic control through dietary management is crucial for preventing complications related to lactic acidosis in GSD I 2
• Continuous feeds (introduced in the 1970s) and cornstarch therapy (introduced in the 1980s) have significantly improved the management of lactic acidosis in GSD I 2

Important Clinical Considerations

• The presence of lactic acidosis is a key distinguishing feature when differentiating GSD I from other types of glycogen storage diseases 1
• Metabolic acidosis in GSD I can be exacerbated during periods of fasting or stress 3
• In patients with GSD undergoing anesthesia, close monitoring of acid-base status is essential as lactic acidosis may develop, particularly during major surgical procedures 4
• Dietary therapy plays a crucial role in minimizing lactic acidosis and improving quality of life in patients with GSD I 3

Diagnostic Approach

• When evaluating a patient with suspected GSD, the presence of lactic acidosis strongly suggests GSD type I rather than other types 1
• The combination of hypoglycemia, lactic acidosis, hepatomegaly, and hyperlipidemia should prompt consideration of GSD I 5
• Molecular genetic testing can confirm the diagnosis of specific GSD types without the need for invasive liver biopsy 1
• Disorders of gluconeogenesis can also present with hyperlacticacidemia and should be considered in the differential diagnosis 1