STEPTRACKERBIOCHEMISTRY + PEDIATRICS + ENDOCRINOLOGY | CARBOHYDRATE METABOLISM | HIGH-YIELD REVIEW

Fructose, Galactose & Sorbitol

Two dietary sugars with a benign kinase defect and a dangerous downstream defect each — plus the polyol pathway that damages diabetic tissues.

FOCUS ON
Kinase defects are benign (sugar spills into urine): essential fructosuria (fructokinase), galactokinase deficiency (cataracts only). The next enzyme down is dangerous because phosphate gets trapped: hereditary fructose intolerance (aldolase B) and classic galactosemia (GALT) → hypoglycemia, liver failure, vomiting; galactosemia → E coli sepsis, cataracts, ID. Both: urine reducing sugar, glucose oxidase test negative. Aldose reductase: glucose → sorbitol → osmotic damage (lens, nerves, retina, kidney).
DISORDER
ENZYME · INHERITANCE
FEATURES
CLUE · TREATMENT
Essential fructosuria
Fructokinase · AR
Asymptomatic; fructose in blood and urine
Benign — hexokinase handles some fructose
Hereditary fructose intolerance
Aldolase B · AR
Starts when weaned onto fruit, juice, sucrose: vomiting, hypoglycemia, jaundice, hepatomegaly, cirrhosis; fructose-1-P traps phosphate
↓ Phosphate → ↓ glycogenolysis and gluconeogenesis · remove fructose, sucrose, sorbitol
Galactokinase deficiency
Galactokinase · AR
Galactose in blood/urine; infantile cataracts (galactitol); may fail to track objects or smile socially
Mild; remove galactose
Classic galactosemia
Galactose-1-P uridyltransferase · AR
Starts with breast milk/formula: vomiting, jaundice, hepatomegaly, hypoglycemia, cataracts, ID, E coli sepsis
Newborn screen · remove galactose and lactose; long-term ovarian failure risk
Aldose reductase (polyol pathway)
Glucose → sorbitol (NADPH); sorbitol DH → fructose
Tissues lacking sorbitol DH accumulate sorbitol: lens, retina, Schwann cells, kidney
Diabetic cataracts, neuropathy, retinopathy
Seminal vesicles & liver
Have both enzymes → convert sorbitol to fructose
Fructose fuels sperm
—
Lactase deficiency
Brush-border lactase ↓ (primary, age-related; secondary after gastroenteritis, celiac)
Bloating, cramps, flatulence, osmotic diarrhea after dairy
↑ Breath hydrogen, ↓ stool pH, normal biopsy · avoid dairy, lactase tablets
Fructose metabolism
Fructokinase → F-1-P → aldolase B → DHAP + glyceraldehyde
Bypasses PFK-1 → enters glycolysis fast
High-fructose loads → fatty liver, ↑ uric acid
Galactose metabolism
Galactokinase → Gal-1-P → GALT (+ UDP-glucose) → glucose-1-P
Galactitol forms via aldose reductase when galactose is high
—

Mechanism — benign first step, dangerous second step

Fructose
→
Fructokinase(essential fructosuria — benign)
→
F-1-PAldolase B blocked → phosphate trapped
Galactose
→
Galactokinase(cataracts only)
→
Gal-1-PGALT blocked → toxic buildup

Trapped phosphorylated sugar is what poisons the liver; an unphosphorylated sugar just spills into the urine.

Sugar disorders compared

DISORDER
ONSET
HYPOGLYCEMIA
CATARACTS
Essential fructosuria
Incidental
No
No
Fructose intolerance
Weaning
Yes
No
Galactokinase ↓
Infancy
No
Yes
Classic galactosemia
First feeds
Yes
Yes

How it's tested

COMMON CONFUSIONTiming tells them apart: symptoms with the first milk feeds → galactosemia; symptoms after starting fruit or juice → hereditary fructose intolerance.
THE TRAPA newborn with jaundice, cataracts and gram-negative sepsis → galactosemia; the bacterium is classically E coli.
YOUR APPROACHWhich sugar triggered it (milk vs fruit)? Is it the kinase (benign) or the next enzyme (toxic)? Then cataracts, hypoglycemia and liver signs confirm.

If you see… think…

Fructose in urine, healthy child → essential fructosuria
Vomiting and hypoglycemia after starting fruit juice → hereditary fructose intolerance (aldolase B)
Infant cataracts only, otherwise well → galactokinase deficiency
Newborn with jaundice, cataracts, E coli sepsis → classic galactosemia (GALT)
Diabetic cataracts and neuropathy → sorbitol accumulation (aldose reductase)
Tissues lacking sorbitol dehydrogenase → lens, retina, Schwann cells, kidney
Bloating after dairy, ↑ breath hydrogen → lactase deficiency
Diarrhea after gastroenteritis worsened by milk → secondary lactase deficiency
Reducing sugar in urine, glucose oxidase strip negative → non-glucose sugar (fructose/galactose)
Sugar that fuels sperm → fructose (seminal vesicles)