Inborn errors of carbohydrate metabolism

Glycogen storage diseases, Congenital galactosaemia, Galactokinase deficiency, Essential fructosuria, Hereditary fructose intolerance, Essential pentosuria

1. Inborn Errors of Carbohydrate Metabolism R. C. Gupta Professor and Head Department of Biochemistry National Institute of Medical Sciences Jaipur, India

2. E M B - R C G

3. E M B - R C G The defect occurs due to a mutation in the gene encoding the enzyme Due to mutation, the enzyme is either catalytically inactive or it has decreased catalytic activity

4. EMB-RCG

5. E M B - R C G When an enzyme in a metabolic pathway is absent or deficient, the entire pathway becomes abnormal Such abnormalities sometimes occur in metabolic pathways involving carbohydrates The resulting diseases are known as inborn errors of carbohydrate metabolism

6. EMB-RCG Major inborn errors of carbohydrate metabolism are: Glycogen storage diseases Congenital galactosaemia Galactokinase deficiency Essential fructosuria Hereditary fructose intolerance Essential pentosuria

7. Glycogen storage diseases EMB-RCG

8. E M B - R C G

9. Hypoglycaemia and muscular weakness can occur due to decreased availability of glucose In some of the diseases, ketosis can also occur The a ffected organs may be enlarged or damaged due to excessive deposition of glycogen EMB-RCG

10. E M B - R C G Glycogen storage disease, Type I

11. E M B - R C G The clinical abnormalities are: Fasting hypoglycaemia Lactic acidosis Hyperlipidaemia Enlargement of liver Retardation of growth Hyperuricaemia and gout can occur around puberty

12. E M B - R C G

13. E M B - R C G Glycogen storage disease, Type II

14. E M B - R C G Pompe’s disease results in progressive: Muscular weakness Hypotonia Cardiomegaly Congestive heart failure

15. E M B - R C G

16. E M B - R C G Glycogen storage disease, Type III

17. E M B - R C G Glycogenolysis stops at the branch points The product of glycogenolysis is limit dextrin Limited dextrin is deposited in tissues Therefore, this disease is also known as limit dextrinosis

18. E M B - R C G Clinical features of Cori’s disease include: Hypoglycaemia Hepatomegaly Muscle weakness Muscle atrophy Retardation of growth

19. E M B - R C G

20. E M B - R C G Glycogen storage disease, Type IV

21. E M B - R C G

22. E M B - R C G The defect is usually present in liver Liver involvement results in : Hepatomegaly Cirrhosis of liver Growth retardation Hepatic failure

23. E M B - R C G In some patients, muscles are also affected Muscle involvement leads to: Hypotonia Muscle weakness Muscle atrophy No effective treatment is known

24. E M B - R C G Glycogen storage disease, Type V

25. E M B - R C G

26. E M B - R C G Glycogen storage disease, Type VI

27. E M B - R C G Hypoglycaemia and hepatomegaly are the usual clinical abnormalities Mild ketosis may also occur Frequent feeding of carbohydrates prevents the symptoms The condition improves with age

28. E M B - R C G Glycogen storage disease, Type VII

29. E M B - R C G

30. E M B - R C G

31. E M B - R C G

32. E M B - R C G

33. E M B - R C G The genetic defect leads to: Severe deficiency of phospho-fructokinase in muscles Moderate deficiency of phospho-fructokinase i n erythrocytes

34. E M B - R C G

35. E M B - R C G Exercise after a carbohydrate-rich meal causes more severe symptoms because: The unutilized glucose inhibits lipolysis Muscles are deprived of glucose as well as fatty acids Avoiding vigorous exercise prevents muscle pain

36. E M B - R C G Glycogen storage disease, Type VIII

37. E M B - R C G

38. E M B - R C G Congenital galactosaemia

39. E M B - R C G

40. E M B - R C G

41. E M B - R C G

42. E M B - R C G Galactokinase deficiency

43. E M B - R C G

44. E M B - R C G

45. E M B - R C G Hereditary fructose intolerance

46. E M B - R C G

47. E M B - R C G

48. E M B - R C G

49. E M B - R C G Essential pentosuria

50. Thank you