Galactose-1-phosphate uridyltransferase (GALT) deficiency causes classic galactosemia. The mechanism of cataracts in galactosemia is DIFFERENT from that in galactokinase deficiency because in GALT deficiency:

• A Galactose-1-phosphate accumulates and directly inhibits glucose phosphate isomerase in the lens
• B Excess UDP-galactose incorporation into glycoproteins of the lens alters their refractive index
• C GALT deficiency prevents galactose from being phosphorylated, so more galactose is available for aldose reductase, producing more galactitol than in galactokinase deficiency
• D Both galactitol (from aldose reductase acting on galactose) AND galactose-1-phosphate accumulate; the latter causes additional toxicity to hepatocytes and brain not seen in galactokinase deficiency ✓

Explanation

In galactokinase deficiency, galactose accumulates and is converted to galactitol by aldose reductase; galactitol cannot be metabolized, accumulates in the lens (osmotic damage), causing cataracts. In GALT deficiency, galactose-1-phosphate (G1P) also accumulates because it cannot be converted to UDP-galactose; G1P is the primary toxic metabolite causing liver damage (jaundice, cirrhosis), brain injury (intellectual disability), and sepsis risk (E. coli). Cataracts from galactitol also occur in GALT deficiency. Thus GALT deficiency has wider systemic toxicity from G1P accumulation, explaining why galactokinase deficiency causes only cataracts while GALT deficiency causes multi-organ involvement.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.