Galactose and Lactose Metabolism😊

Feature
Classical Galactosemia
Hereditary Fructose Intolerance (HFI)
Enzyme Defect
Galactose-1-Phosphate Uridyltransferase
Aldolase B
Age of Onset
1st week of life
(Immediately in neonates)
Around 6 months
(While Weaning)
Trigger
Breastfeeding
Fruits
Specific Test
Mucic acid test: Positive
Rapid Fural / Seliwanoff's Test: Positive
Cataracts
Present due to galactitol
NO CATARACT
Symptoms
• Intellectual disability, cataracts
• jaundice, hepatomegaly, failure to thrive
• Hypoglycemia, no cataracts
• vomiting, jaundice, hepatomegaly,
Accumulated Compound
Galactose-1-P, galactitol
Fructose-1-P
Glucose Oxidase Test
Negative
Negative
Urine Benedict's Test
Positive
Positive
Treatment
Lactose-free diet
(galactose & lactose restriction)
Fructose-free diet

Intolerences and ages

  • Immediately in neonates
    • Galactosemia
    • Lactose intolerence
  • While Weaning
    • Fuctose intolerence
  • In young children
    • Celiac disease

Galactose Metabolism

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Galactose → enters cells

  • GLUT transporter
  • by passive diffusion.

Steps of Galactose Metabolism

  1. Galactose → Galactose 1 Phosphate
      • by Galactokinase.
  1. Galactose 1 Phosphate → UDP Galactose
      • by Galactose-1-Phosphate Uridyl Transferase (GalPUT).
      • Produce UDP galactose
        • Active form of galactose.
        • Used in anabolic pathways:
          • Synthesis
            • Keratan sulphate
            • Myelin
            • Ganglioside
  1. Excess UDP galactose → UDP glucose
      • by Epimerase.
      • UDP glucose
        • Active form of glucose.
        • Used for glycogen synthesis.

Summary

  • All Autosomal recessive (AR)
  • Enzyme in classic = GalPUT.
  • Cataract without hepatomegaly = Galactokinase deficiency.
  • E. coli sepsis strongly linked with galactosemia.
  • Reducing sugar in urine but not glucose
    • think galactosemia/hereditary fructose intolerance.
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Type
Enzyme Deficient
Key Features
Classical
GalPUT
• Positive Benedict's test
• Bilateral congenital cataracts (Oil drop cataract)
• Low phosphate levels
• Fasting Hypoglycemia
• Exercise intolerance
• Jaundice, Hepatomegaly
• Uric acid + lactic acidosis
• E. coli sepsis.
• Premature ovarian failure
• Breast milk absolutely Contraindicated
Non-Classical
Galactokinase
• Positive Benedict's test
• Bilateral congenital cataracts (Oil drop cataract)
• NO HEPATOMEGALY
Epimerase
Epimerase
Variable symptoms
  • Mnemonic: Galact (GALT) Galact (Galactokinase) Appi (Epimerase)

Galactokinase Defect

  • Non-Classical Galactosemia
  • Cataract without hepatomegaly = Galactokinase deficiency.
  • Galactose effluxes into circulation
    • Galactosemia
    • Appears in urine.
      • Positive Benedict's test
      • (galactose is a reducing sugar).
  • Excess galactose enters lens fibers
    • galactose → galactitol (dulcitol).
      • By Aldose reductase
      • Galactitol
        • trapped & cannot leave the lens
        • Osmotic movement of water → lens swells
          • cataract formation (Oil drop cataract).

GalPUT (Galactose-1-phosphate Uridyl Transferase) Defect

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  • Classical galactosemia.
  • Puttu (GalPUT) kandu vanna Puucha (Cat → Cataract) Acid (Lactic acid, uric acid) thatti ittu newborn () nte mukalil → sepsis kolam (E coli sepsis) ayi → POI (POF)
  • 2 main events
    • Galactose accumulation
      • Galactose-1-phosphate → â›” galactokinase (feedback)
        • Positive Benedict's test in urine.
        • Cataract formation.
    • Hypophosphatemia occurs
      • Galactose-1-phosphate → trapped inside the cell
        • low phosphate levels.
        • Muscle and Hepatic Glycogen phosphorylase
          • Require Inorganic Phosphate
          • Fasting Hypoglycemia
          • Exercise intolerance
        • Impairs the ADP → ATP.
          • ATP deficiency in cells
          • When hepatocytes have ATP deficiency, it causes:
            • Jaundice.
            • Hepatomegaly.
      • Unwanted ADP
        • uric acid + lactic acidosis.
  • Neonates
    • susceptible to E. coli neonatal sepsis.
  • Female children
    • suffer from premature ovarian failure.
  • Breast milk absolutely Contraindicated
    • Lactose (galactose + glucose),
      • issues in mother-fed babies.
A 22-year-old male who had diarrhoea and a dairy intolerance was seen. He was later diagnosed with lactase deficiency. Which of the following agents is least likely to result in lactose intolerance?
  1. Condensed milk
  1. Skimmed milk
  1. Yoghurt
  1. Ice cream
      2. ANS
      1. Yoghurt

Fructose Metabolism

Site: Liver

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1. Essential Fructosuria

  • Autosomal recessive
  • Enzyme Defect:
    • Fructokinase
  • Pathophysiology:
    • Fructose not trapped in cells → hexokinase converts small amounts to fructose-6-P
  • Symptoms:
    • Benign, asymptomatic
    • Fructosuria
      • NO FRUCTOSEMIA
  • Diagnosis:
    • Urine dipstick negative (only detects glucose)
    • Benedict’s test positive in urine
  • Treatment:
    • None required

2. Hereditary Fructose Intolerance (HFI)

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  • (autosomal recessive)
  • Enzyme Defect:
    • Aldolase B
  • Pathophysiology:
    • Fructose-1-P accumulates → ↓ inorganic phosphate
      • → â›” of glycogenolysis and gluconeogenesis
  • Symptoms:
    • Begin after
      • Intake of fruit juice, honey, or sucrose
      • Weaning period
    • Hypoglycemia, jaundice, vomiting
    • Failure to thrive, hepatomegaly, cirrhosis
    • NO cataracts
  • Glucose Oxidase Test: Negative
  • Urine Benedict's Test: Positive
  • Specific Test: Rapid Fural Test / Seliwanoff’s Test: Positive
  • Diagnosis: Enzyme studies & genetic mutation test
  • Treatment:
    • Avoid fructose, sucrose, and sorbitol

Sorbitol Pathway

  • Normally inactive.
  • Activated by hyperglycemia
      1. T1DM > T2DM
      1. Galactosemia
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Tissues

  • Aldose reductase + Sorbitol dehydrogenase present
    • Liver, ovaries, seminal vesicles
    • No accumulation of sorbitol
    • Mnemonic: LOSe sorbitol
  • Only aldose reductase
    • Lens, Retina, Kidneys, Schwann cells (LRKS)
    • Application
      • Diabetes
        • Sorbitol accumulation → Carbamylation of crystallins
          • Snowflake Cataracts (Cortical cataract)
          • Retinopathy
          • Neuropathy
          • Nephropathy
      • Classical Galactosemia
        • High galactose → Galactitol (via aldose reductase) → osmotic damage
        • Oil drop cataract