What is the cause of lactic acidosis in Von Gierke's (Glycogen Storage Disease Type I) disease?

From the Guidelines

Lactic acidosis in Von Gierke's disease (glycogen storage disease type I) occurs primarily due to impaired gluconeogenesis, resulting from a deficiency of glucose-6-phosphatase, which prevents the liver from converting glycogen to glucose and from performing gluconeogenesis effectively. The disease is caused by a deficiency of glucose-6-phosphatase, which is a key enzyme in the regulation of blood glucose levels, as noted in the study by 1. When blood glucose levels fall, the body cannot properly release glucose from the liver, leading to hypoglycemia. In response, the body shifts to anaerobic metabolism, producing excess lactic acid. Additionally, the accumulation of glucose-6-phosphate in liver cells inhibits the enzyme phosphorylase, further blocking glycogen breakdown. The metabolic acidosis is worsened by impaired clearance of lactic acid, as pyruvate cannot be efficiently converted back to glucose through gluconeogenesis. This creates a vicious cycle where hypoglycemia triggers more lactic acid production, while the inability to metabolize pyruvate causes further lactic acid accumulation.

The clinical presentation of GSD I, as described in the study by 1, includes symptoms such as hyperpnea due to lactic acidosis, which may simulate that occurring in pneumonia. Patients may also present with hepatomegaly, protuberant abdomen, and failure to thrive. The study by 1 notes that the presenting symptoms of GSD Ia vary according to the patient's age, with patients presenting during the neonatal period with hypoglycemia and lactic acidosis, or at 3 to 6 months of age with hepatomegaly and/or signs and symptoms of hypoglycemia.

Management of GSD I focuses on preventing hypoglycemia through frequent carbohydrate intake, cornstarch therapy, and sometimes continuous nocturnal gastric drip feedings to maintain glucose levels and reduce lactic acid production. The study by 1 highlights the importance of preventing hypoglycemia, as recurrent hypoglycemic episodes can cause cerebral damage and delayed motor development. Preventing hypoglycemia is crucial in managing GSD I, as it can help reduce the incidence of lactic acidosis and improve the overall quality of life for patients.

Key points to consider in the management of GSD I include:

• Frequent carbohydrate intake to prevent hypoglycemia
• Cornstarch therapy (1-2 g/kg every 4-6 hours) to maintain glucose levels
• Continuous nocturnal gastric drip feedings to reduce lactic acid production
• Monitoring for complications such as liver adenomas, hepatocellular carcinoma, and renal glomerular dysfunction
• Management of related conditions such as anemia, vitamin D deficiency, and osteoporosis.

From the Research

Cause of Lactic Acidosis in Von Gierke's Disease

The cause of lactic acidosis in Von Gierke's disease can be attributed to the underlying metabolic disorder characterized by a deficiency in glucose-6-phosphatase activity 2, 3. This deficiency leads to an inability to convert glycogen to glucose, resulting in hypoglycemia and the accumulation of lactate.

Metabolic Pathways Involved

The metabolic pathways involved in the development of lactic acidosis in Von Gierke's disease include:

• Impaired gluconeogenesis due to glucose-6-phosphatase deficiency 3
• Increased lactate production due to anaerobic metabolism 4
• Decreased lactate utilization due to impaired liver function 4

Clinical Presentation

Patients with Von Gierke's disease may present with:

• Hypoglycemia 2, 3, 5
• Lactic acidosis 2, 6, 4
• Hepatomegaly 2, 3
• Growth retardation 3
• Renal involvement 3

Treatment and Management

Treatment and management of lactic acidosis in Von Gierke's disease involve:

• Dietary therapy to avoid hypoglycemia and acidosis 2, 5
• Frequent feedings and nocturnal enteral feeding 5
• Restricted fructose and galactose intake 3
• Liver transplantation in cases of poor metabolic control or hepatocarcinoma 3