Parents bring their -month-old daughter to the acute care clinic due to episodes of profound sweating, vomiting, and unresponsiveness. According to the parents, the infant was entirely asymptomatic during her first few months of life while being exclusively breastfed. However, following the introduction of fruit purees and apple juice three weeks ago, she began having these episodes shortly after feeding. Vital signs include a heart rate of /min and a respiratory rate of /min. Physical examination demonstrates a pale, difficult-to-arouse infant with marked hepatomegaly.
The following laboratory findings are reported:
| Laboratory Test | Result | Reference Range |
|---|---|---|
| Capillary blood glucose | mg/dL | - mg/dL |
| Serum lactate | mmol/L | - mmol/L |
| Serum uric acid | mg/dL | - mg/dL |
| Urinalysis (glucose oxidase) | Negative | Negative |
| Urinalysis (reducing substances) | Positive | Negative |
Which of the following is the most likely underlying biochemical defect in this patient?
- ADecreased fructokinase activity
- BAccumulation of galactose-1-phosphate
- Impaired cleavage of fructose-1-phosphateAnswer
- DDefective transport of glucose-6-phosphatase
- EImpaired conversion of pyruvate to acetyl-CoA
Answer
Impaired cleavage of fructose-1-phosphate
The correct answer is impaired cleavage of fructose-1-phosphate, which causes hereditary fructose intolerance (Aldolase B deficiency). This autosomal recessive condition typically presents when fructose-containing foods (such as fruit purees and juices) are first introduced into an infant's diet, usually around to months of age. The deficiency of Aldolase B leads to an accumulation of fructose-1-phosphate in the liver, which depletes intracellular ATP and inorganic phosphate. This depletion ultimately inhibits both glycogenolysis and gluconeogenesis, resulting in severe hypoglycemia. Clinical manifestations include recurrent vomiting, diaphoresis, lethargy, and hepatomegaly following meals. Laboratory tests classically show hypoglycemia, lactic acidosis, hyperuricemia, and the presence of fructose in the urine, which is detected as a positive non-glucose reducing substance.
Step-by-Step Solution
Key Concept
Hereditary fructose intolerance (Aldolase B deficiency) presents with severe hypoglycemia, lactic acidosis, hepatomegaly, and vomiting following the dietary introduction of fructose (e.g., fruit purees, juices). It typically causes non-glucose reducing substances to appear in the urine.