History:

A 14-month-old child is below the 8th percentile for age in height and 25th percentile in weight. He has had periodic convulsions. On the last of these episodes, which followed a feeding of milk and applesauce, the serum glucose was found to be 27 mg/dL. Additional laboratory findings include serum triglyceride 410 mg/dL, total cholesterol 292 mg/dL, lactate 5.5 mmol/L, and uric acid 11.2 mg/dL. On examination, the child has a very cute, doll-like appearance with prominent cheeks and a protuberant abdomen. An abdominal CT scan reveals an enlarged liver and kidneys.

The liver shows fatty change. There is abundant glycogen. The laboratory findings show hypoglycemia (in spite of the recent feeding), hyperlipidemia, elevated lactate, and hyperuricemia.

Answers:

1. What disorder is most likely represented by these findings?

The findings suggest a glycogen storage disease involving the liver and kidneys. This is glycogenosis type I. A definitive diagnosis is made by genetic testing. There are over 2 dozen known mutations, but several are common, and the R83C mutation is the most common, particularly in Jewish populations. White blood cells or chorionic villus cells can be tested.

2. Explain the biochemistry of this disorder.

Normally, glycogen phosphorlyase cleaves the end of the chain of the storage carbohydrate glycogen, yielding glucose-1-phosphate which is then transformed to glucose-6-phosphate. In von Gierke disease, the enzyme glucose-6-phosphatase required for the next step is lacking. Thus, the glucose-6-phosphate is not metabolized to glucose.

3. Explain the findings.

The inability to metabolize glycogen results in increased glycogen stores, particularly in hepatocytes and renal tubular epithelium. Lipid and protein metabolism are altered to provide an energy source in lieu of glucose. Growth is stunted. Altered lipid metabolism leads to hyperlipidemia and fatty metamorphosis of the liver, resulting in hepatomegaly. Increased turnover of protein leads to increased uric acid production. Inability to provide glucose in stressful circumstances leads to anaerobic glycolysis with elevated blood lactate and hypoglycemia. Fructose and galactose cannot be properly utilized and can precipitate a hypoglycemic episode.

4. How is this disease treated?

Frequent feedings with glucose are needed.

5. What are complications of this disease?

Long-term complications of Von Gierke disease include gout from the hyperuricemia, tumors of the liver (hepatic adenoma, hepatocellular carcinoma), osteoporosis, kidney stones (uric acid), and kidney failure.