Hereditary Fructose Intolerance

Question 1

A 6-month-old infant is brought to the emergency department due to vomiting, lethargy, and sweating. The symptoms started shortly after the introduction of fruit juice into the diet. Physical examination reveals jaundice, hepatomegaly, and poor weight gain. Laboratory studies show severe hypoglycemia, elevated liver transaminases, and prolonged prothrombin time (PT). Urinalysis reveals the presence of reducing substances, but glucose testing is negative. Which of the following is the most likely deficient enzyme in this condition?

A) Fructokinase
B) Aldolase B
C) Glucose-6-phosphatase
D) Galactose-1-phosphate uridyltransferase
E) Hexokinase

Answer 1

Answer: B) Aldolase B

Explanation: Hereditary Fructose Intolerance (HFI) is caused by a deficiency of Aldolase B, an enzyme that converts fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate in the liver. Accumulation of fructose-1-phosphate leads to depletion of phosphate stores, resulting in inhibition of glycogenolysis and gluconeogenesis, which causes severe hypoglycemia. Symptoms often present after the introduction of sucrose or fructose-containing foods into the diet, such as fruit juice. Key findings include jaundice, hepatomegaly, vomiting, and reducing substances in urine.

Incorrect Answers:

A) Fructokinase deficiency causes Essential Fructosuria, a benign condition with no hypoglycemia or hepatomegaly.
C) Glucose-6-phosphatase deficiency causes Von Gierke disease, characterized by severe fasting hypoglycemia and lactic acidosis.
D) Galactose-1-phosphate uridyltransferase deficiency leads to classic galactosemia, with cataracts and hepatomegaly but not hypoglycemia due to fructose ingestion.
E) Hexokinase is not involved in fructose metabolism in this context.

Question 2

What is the incidence of Hereditary Fructose Intolerance?

Answer 2

Up to 1:18,000 live births

Question 3

What is the gene defect associated with Hereditary Fructose Intolerance?

Answer 3

Mutation in the gene on chromosome 9q

Question 4

What enzyme is deficient in Hereditary Fructose Intolerance?

Answer 4

Aldolase B

Question 5

What is the normal function of Aldolase B?

Answer 5

Converts fructose-1-phosphate to glyceraldehyde and dihydroxyacetone phosphate

Question 6

What is the effect of Aldolase B deficiency in Hereditary Fructose Intolerance?

Answer 6

Accumulation of fructose-1-phosphate, leading to depletion of available phosphates, inhibition of glycogenolysis and gluconeogenesis, and severe hypoglycemia

Question 7

When do symptoms of Hereditary Fructose Intolerance typically present?

Answer 7

Symptoms begin within the first months of life after the introduction of sucrose or fructose-containing foods

Question 8

What are the key clinical features of Hereditary Fructose Intolerance?

Answer 8

Bloating, sweating, vomiting, failure to thrive, jaundice, severe hypoglycemia (seizures, irritability, cyanosis), hepatomegaly, and renal tubular dysfunction

Question 9

How is Hereditary Fructose Intolerance diagnosed?

Answer 9

Detection of reducing substances (fructose) in urine

definitive diagnosis via enzyme assay in a liver biopsy or genetic testing

Question 10

What is the main treatment for Hereditary Fructose Intolerance?

Answer 10

Lifelong adherence to a fructose-free, sorbitol-free, and sucrose-free diet