Von Gierke Disease Flashcards
A 6-month-old infant is brought to the emergency department due to lethargy and seizures. The parents report that the child becomes irritable and weak several hours after feeding. Physical examination reveals doll-like facies, hepatomegaly, and a protuberant abdomen. Laboratory studies show severe hypoglycemia, hypertriglyceridemia, lactic acidosis, and hyperuricemia. Genetic testing identifies a mutation in the G6PC gene. Which of the following is the most likely cause of the infant’s symptoms?
A) Impaired glucose transport into the endoplasmic reticulum
B) Deficiency of glucose-6-phosphatase activity
C) Deficiency of glycogen phosphorylase activity
D) Excessive gluconeogenesis
E) Increased glycogenolysis
Answer: Deficiency of glucose-6-phosphatase activity
Explanation: Von Gierke disease (Type 1a glycogen storage disease) is caused by a deficiency of glucose-6-phosphatase, an enzyme responsible for converting glucose-6-phosphate into glucose in the liver and kidneys. This deficiency impairs glycogenolysis and gluconeogenesis, leading to severe fasting hypoglycemia. The inability to generate free glucose results in metabolic derangements such as hypertriglyceridemia, lactic acidosis, and hyperuricemia. Organomegaly (Hepatomegaly and Renomegaly) occurs due to glycogen accumulation in the liver and kidneys. Diagnosis is confirmed with genetic testing identifying mutations in the G6PC gene.
Incorrect Answers:
A) Impaired glucose transport into the endoplasmic reticulum is the defect in Type 1b Von Gierke disease, not Type 1a.
C) Deficiency of glycogen phosphorylase activity is seen in glycogen storage disease Type V (McArdle disease), which primarily affects skeletal muscle.
D) Excessive gluconeogenesis would increase glucose production, which is not seen in Von Gierke disease.
E) Increased glycogenolysis would release free glucose, alleviating hypoglycemia, which is not the case in this disease due to the enzymatic defect.
What is the gene defect and deficient enzyme in Type 1a Von Gierke disease?
Mutation in the G6PC gene on chromosome 17q; deficient enzyme is glucose-6-phosphatase
What is the role of glucose-6-phosphatase in Type 1a Von Gierke disease?
Hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate
What are the characteristic clinical features of Type 1a Von Gierke disease?
Hepatomegaly, severe fasting hypoglycemia, hyperlipidemia (especially triglycerides), hyperuricemia, lactic acidosis, failure to thrive
What is the gene defect and deficient enzyme in Type 1b Von Gierke disease?
Mutation in the SLC37A4 gene on chromosome 11q; deficient enzyme is glucose-6-phosphate translocase
What is the role of glucose-6-phosphate translocase in Type 1b Von Gierke disease?
Transport of glucose-6-phosphate into the endoplasmic reticulum for hydrolysis by glucose-6-phosphatase
What are the characteristic clinical features of Type 1b Von Gierke disease?
Doll-like facies.
Thin upper extremities.
Hepatosplenomegaly, severe fasting hypoglycemia, hyperlipidemia, hyperuricemia, lactic acidosis, anemia, failure to thrive, dysfunctional glycogenolysis and gluconeogenesis
What metabolic abnormalities are common to both Type 1a and Type 1b Von Gierke disease?
Severe fasting hypoglycemia, hyperlipidemia, hyperuricemia, lactic acidosis
What are potential long-term complications of Von Gierke disease?
Hepatic adenomas, increased risk of gout, growth failure, renal dysfunction
What dietary modifications are crucial in managing Von Gierke disease?
Frequent feeding with cornstarch to prevent hypoglycemia, avoidance of fructose and galactose to reduce metabolic stress
