Retrospective Case Series of Fulminant Metabolic Crisis in GSDIA: Persistent Lactic Acidosis Despite Correction of Hypoglycemia May Reflect Secondary Mitochondrial Dysfunction

In people with glycogen storage disease type Ia, treatments that normalize blood sugar do not always eliminate lactic acidosis, showing that other metabolic factors besides low glucose contribute to this condition.

Some people with glycogen storage disease type Ia have high lactate levels in their blood even when their blood sugar is normal, because their mitochondria cannot remove lactate effectively, which disrupts metabolic balance.

Patients with glycogen storage disease type Ia have abnormal levels of specific metabolic compounds in their blood and urine, showing that their entire metabolism is disrupted in ways that go beyond just trouble making glucose.

In patients with glycogen storage disease type Ia experiencing acute metabolic crisis, thiamine supplementation is associated with lower lactic acid levels, as observed in one case where lactate normalized after high-dose thiamine was given, though extracorporeal membrane oxygenation may have influenced the result.

Metabolic acidosis disrupts the proton gradient across mitochondrial membranes, which decreases the efficiency of ATP production.

In people with glycogen storage disease type Ia, mitochondrial dysfunction worsens over time and leads to long-term organ damage such as liver tumors, kidney disease, and failure of multiple organs, regardless of acute metabolic episodes.