Disorders of Carbohydrate Metabolism GALACTOSEMIA

1. Disorders of Carbohydrate MetabolismGALACTOSEMIA

3. Disorders of Carbohydrate Metabolism • Problems processing simple sugars galactose and fructose, or glycogen storage diseases • Summary of disorders and clinical symptoms are found in the following table

4. G A L A C T O S E M I A • Galactosemiais an inherited recessive deficiency in enzymes that metabolize galactose • Galactosemia= high level of plasma galactose.

5. Introduction • Galactosemia is an autosomal- recessive disorder. 1 in 60 000 newborns are diagnosed with Galactosemia every year

6. What is Galactose? • Galactose is a monosaccharide. • Lactose is a sugar that is found in many foods. When lactose is broken down in the body, glucose and galactose are produced. • Foods that contain galactose and lactose include: fruits, vegetables, legumes, organ meats, processed meats and sandwich meats, milk and dairy products, coffee

8. M I L Kthe primary source of galactose http://learn.genetics.utah.edu/units/disorders/whataregd/galactosemia/images/galacpthwy.jpg

9. GALACTOSE METABOLISM

10. GALT NORMAL GALACTOSE METABOLISM • Dietary lactose is digested into glucose and galactose, and absorbed through the intestine • Galactose is taken up by a RBC (carrier-mediated), it is phosphorylated to Galactose-1-Phosphate (Gal-1-P) by Galactokinase(GALK) • Gal-1-P is converted to Glucose-1-Phosphate(Glu-1P) using the epimerization of UDP-Glucose to UDP-Galactose by the enzyme Galactose-1-Phosphate Uridyl Transferase (GALT).That is: Gal-1-P + UDP-Glucose UDP-Galactose + Glu-1-P • Glu-1-P proceeds on to glycolysis • UDP-Galactose is recycled back to UDP-Glucose by Uridyl Diphosphate Galactose 4-Epimerase(GALE)

11. Glucose & galactose differ only in the orientation of the OH and H on carbon 4 (epimers)

12. THREE TYPES OF GALACTOSEMIA 1. GALT Deficiency Most severe form: “classic galactosemia” Most prevalent: 95% of cases 2. GALK Deficiency • Milder form • 5% of cases 3. GALE Deficiency rare

13. M e c h a n i s m 1. GALT Deficiency • Deficiency in GALT leads to a build up of Gal-1-P and UDP-Glucose.

14. 1. GALT Deficiency • ‘Failure to thrive’ • Jaundice • Vomiting & Diarrhea • Lethargy • Renal dysfunction • Hepatomegaly • Cataract • Sepsis • Ovarian failure • Mental retardation • Death E f f e c t s

15. THREE TYPES OF GALACTOSEMIA 1. GALT Deficiency Most severe form: “classic galactosemia” Most prevalent: 95% of cases 2. GALK Deficiency • Milder form • 5% of cases 3. GALE Deficiency rare

16. M e c h a n i s m 2. GALK Deficiency Deficiency of GALK leads to a build up of galactose which can be converted to toxic galactitol.

17. 2. GALK Deficiency • Cataracts • hypertension (rare) E f f e c t s

18. THREE TYPES OF GALACTOSEMIA 1. GALT Deficiency Most severe form: “classic galactosemia” Most prevalent: 95% of cases 2. GALK Deficiency • Milder form • 5% of cases 3. GALE Deficiency rare

19. M e c h a n i s m • Deficiency in GALE leads to a build up of Gal-1-P and UDP-Galactose cannot be converterted back to UDP-Glucose 3. GALE Deficiency

20. 3. GALE Deficiency • Symptoms similar to classic galactosemia, sometimes with hearing loss. E f f e c t s

21. Blood tests Enzyme activity in RBCs Normal range for Galactose-1-phosphate uridyl transferase activity is18.5 to 28.5 U/g Hb. Low blood sugar (hypoglycemia) Urine analysis Reducing substances accumulation (i.e. galactose & galactose-1-P) DIAGNOSIS T e s t s

22. Signs & Symptoms

23. TREATMENT • No pharmacological treatment is currently available • Sources of galactose (especially lactose) must be eliminated from the diet • All dairy products (chesses, yoghurt, ice cream), breast milk, infant formulas, sweeteners • Foods with > 10mg galactose/100g fresh weight must be avoided; dates, papaya, tomatoes, watermelon • Calcium and vitamin supplementation (vitamin D)