A 6-month-old infant has progressive hepatosplenomegaly, failure to thrive, and cataracts. Reducing substances are found in urine but glucose oxidase test is negative. RBC enzyme assay confirms galactose-1-phosphate uridylyltransferase deficiency. Which metabolite is directly responsible for cataracts in this disorder?
- A Galactose-1-phosphate
- B UDP-galactose
- C Galactitol ✓
- D Galactonate
Explanation
In classic galactosemia (GALT deficiency), accumulated galactose is reduced by aldose reductase to galactitol (a sugar alcohol), which cannot be further metabolized and accumulates in the lens. Galactitol accumulation increases osmotic pressure in the lens, causing fluid influx and cataract formation. Galactose-1-phosphate accumulation is responsible for hepatotoxicity and renal/neurological damage through different mechanisms (inhibiting phosphoglucomutase and other enzymes). Galactonate is a minor oxidative byproduct. This distinction is clinically important: cataracts may be partially reversible with early dietary lactose restriction, while neurological damage from galactose-1-phosphate may be irreversible.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.