MEDizzy - A 2-week-old newborn was brought to the pediatrician due to

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Glycolysis and Gluconeogenesis

A 2-week-old newborn was brought to the pediatrician due to frequent vomiting, lethargy, and diarrhea. Family history revealed that the child never seemed to eat well, and had only been breastfed. Physical examination revealed an enlarged liver and jaundice. The pediatrician was suspicious of an inborn error of metabolism and referred the child to an ophthalmologist for a slit-lamp exam, the result showed classic galactosemia. An enzyme that may be defective in this child is which one of the following?

ExplanationThe answer is B: Galactose-1-phosphate uridylyltransferase. The child has classic galactosemia, a defect in galactose-1-phosphate uridylyltransferase. Due to the accumulation of galactose-1-phosphate, galactokinase is inhibited, and free galactose accumulates within the blood and tissues. The accumulation of galactose in the lens of the eye provides the substrate for aldose reductase, converting galactose to its alcohol form (galactitol). The accumulation of galactitol leads to an osmotic imbalance across the lens, leading to cataract formation. Additionally, the increased galactose-1-phosphate, at very high levels in the liver, blocks phosphoglucomutase activity, resulting in ineffective glucose production from glycogen (phosphorylase degradation of glycogen will produce glucose-1-phosphate, but this cannot be converted to glucose-6-phosphate if phosphoglucomutase activity is inhibited). A defect in galactokinase will lead to nonclassical galactosemia, with cataract formation, but none of the feeding problems associated with classical galactosemia (associated with the accumulation of galactose-1-phosphate) are observed in nonclassical galactosemia. None of the other enzymes listed, if deficient, will give rise to the symptoms produced, particularly cataract formation. A defect in glycogen synthase would lead to reduced glycogen levels and fasting hypoglycemia.