Glycogen storage disorders or diseases are a collection of rare diseases associate with defects in glycogen metabolism.

1. GLYCOGEN STORAGE
DISORDERS
BY DR K.M PARAKRAMA
REG WD 15A 2

2. INTRODUCTION
• Glycogen is a branched-chain polymer of glucose and serves as
a dynamic but limited reservoir of glucose, mainly in skeletal
muscle and liver.
• There are a number of different enzymes involved in glycogen
synthesis, utilization and breakdown within the body.
• Glycogen storage disorders (GSD) are a group of inherited
inborn errors of metabolism due to deficiency or dysfunction of
these enzymes.

3. • confined to just liver and muscle
• But some cause more generalised pathology and affect tissues
such as the kidney, heart and bowel.
• The classification of glycogen storage disorders is based on the
enzyme deficiency and the affected tissue.

5. EPIDIOMOLOGY
• The overall GSD incidence is estimated at 1 case per 20,000-
43,000 live births.
• Type I is the most common (25% of all GSD).

6. INHERITANCE PATTERNS
• Autosomal recessive (I, II, III, IV, V, VII, some IX).
• Both parents are carriers.
• Chance of sibling being affected is 1 in 4.
• X-linked (some IX, VI)

7. TYPES
• There are eleven (11) distinct diseases that are commonly
considered to be glycogen storage diseases
• Although glycogen synthase deficiency does not result in
storage of extra glycogen in the liver, it is often classified with
the GSDs as type 0.

8. TYPE 1 GLYCOGEN STORAGE DISORDER
• Von Gierke's disease
• Absence of deficiency of Glucose 6 Phosphatase or absence of
translocase enzyme (1b)
Both cause fasting hypoglycaemia

9. • Clinical features:-
• Appearance-
• Doll like face(fat cheeks)
• Protuberant abdomen
• Thin extremities
• Renomegaly
• Massive Hepatomegaly
• Milky serum (hypertriglyceridemia), hyperuricaemia, lactic
acidosis
• Heart, Spleen Not Involved

10. • In type 1b,
• Intermittent diarrhoea (disruption of mucosal barrier)
• Neutropenia, recurrent infections (cell aggregation defects)
• Life threatening HMB, easy bruising, epistaxis (platelet aggregation
defects)
• Liver involvement- hepatic adenomas (by 2nd 3rd decade
become malignant)
• Kidney (FSGS, Interstitial fibrosis, Fanconi syndrome, DRTA)
• Pulmonary hypertension
• Increased risk of thyroid autoimmunity

11. • Dx-
• Liver biopsy-fat globules, glycogen globules
• Gene based mutation detection

13. • Rx-
• Omit fructose, sorbitol
• Glucose, corn starch via NG tube
• Overnight drip feeding
• Lipid lowering drugs
• Liver transplant-in latter stages
• GMCSF-to treat neutropenia
• DDAVP

14. TYPE II, POMPE'S DISEASE/ACID MALTASE
DEFICIENCY
• The deficiency of the lysosomal enzyme alpha-1,4- glucosidase
(acid maltase) leads to the accumulation of glycogen in many
tissues.
• Cardiac, skeletal, smooth muscle involvement

15. • Two types
• 1.Infantile
• 2.Late onset
• Infantile-
• Present in weeks-months
• Hypotonia
• Poor feeding
• Macroglossia
• Hepatomegaly
• Bulbar weakness

16. • Hypertrophic cardiomyopathy is lethal in 1st year
• Late onset-
• Less cardiac involvement
• Skeletal dysfunction (1st year-6th decade)
• Proximal muscle weakness (hipgridle, paraspinals, Diaphragm)
• Also, ptosis, lingual deficiencies and dilation of
basilar/ascending aorta can occur
• Death occurs due to respiratory depression and rupture of
basilar vessels

19. • Investigation findings-
• Elevated muscle enzymes(CPK,LDH,AST)
• ECG elevated QRS, decreased PR interval
• Echo-thickened L/R ventricles and septum
• EMG-myopathic features
• Muscle Bx-Vacuoles stained for glycogen

20. • Dx-
• Muscle biopsy, fibroblast culture- Enzyme assay
• Gene sequencing
• Urinary glucose tetrasachcharides increase
• Rx-
• Enzyme replacement-Alglucosidase( can halt/reverse muscle
damage)
• High protein diet
• Nocturnal ventilator support

21. TYPE III, CORI DISEASE DEBRANCHER
DEFICIENCY
• Debranche enzyme breakdown glycogen
• Defect causes accumulation of limit dextrin like substances
• Two types
• 3a-involve muscle, liver
• 3b-iver only

22. • Clinical features of type 1-
• Similar to GSD 1but
• HSM no Renomegaly
• Cardiomyopathy
• Hepatic symptoms improve with age/may progress to cirrhosis
or hepatic failure
• Hepatic carcinoma risk is less than type 1
• Myopathy-
• can present in childhood
• Severe in 3rd 4th decade
• No pattern in involvement

23. • Cardiomyopathy-ventricular dysfunction is rare/Arrhythmias
can occur
• PCOS with hirsutism, fertility is preserved
• Hypoglycaemia
• Hyperlipidaemia
• Elevated AST/ALT
• Fasting ketosis Urates are normal
• Muscle kinases are elevated

25. • Dx-
• Liver biopsy-distended hepatocytes
• Demonstration of enzyme activity in liver and muscle
• Mutation analysis
• Rx-
• Frequent high protein high caloric meals
• Liver/cardiac transplant

26. TYPE IV, ANDERSEN'S DISEASE,
AMYLOPECTINOSIS
• Deficiency of branching enzyme
• Accumulation of non soluble glycogen similar to amylopectines
• If totally deficient, can cause perinatal death

27. • Clinical features-
• 4 variants
• Perinatal-foetal akinesia/death
• Congenital-present at birth
Hypotonia/muscle atrophy
• Childhood variant-myopathy
cardiomyopathy
• Adult-deposition of polyglucosan
peripheral nerve involvement

28. • Commonest presentation-progressive hepatic cirrhosis at 18
months
• Death by 5 yrs
• Dx-
• Electron microscopy-fibrillary material similar to amylopectines
• Demonstration of reduced enzyme
activity(liver,muscle,fibroblasts)
• Genetic studies
• Rx-??(multi systemic disease place of liver transplant)

29. TYPE V, MCARDLE'S DISEASE
• Myophosphorylase deficiency
• Needed in glycogen degradation
• Decreased muscle ATP, accumulation of glycogen in muscles

30. • Symptoms-
• Easy fatigability
• Exercise intolerance
• Pain
• Respiratory complications
• “second wind”-stop as pain occurs then can go for a prolonged
duration
• 35% develop pain at rest
• Can cause ARF due to rhabdomyolisis

32. • Ix-
• CPK at rest
• S.Lactate, Uric acid and ammonia will rise with excersise
• Dx-
• Muscle enzyme activity measurement
• Muscle bx to asses Glycogen
• Phosphorus MRI to see excessive reduction of phospho
creatinine with excersise

33. • Rx-
• Decrease exercise strenuity
• Glucose, sucrose to be given prior to exercise
• Glucagon before exercise
• LONGEVITY IS NOT AFFECTED

34. TYPE VI, HERS DISEASE
• Affected enzyme: Liver phosphorylase.
• Benign course
• Hepatomegaly with growth retardation in early childhood
• Some, hypoglycaemia, hyperlipidaemia, hyperketosis
• Lactic, uric acid levels normal
• Heart, skeletal muscles not involved

35. • Hepatomegaly, growth retardation improve with age
• Rarely post prandial lactic acidosis
• Dx-
• Molecular testing
• Liver bx
• Rx-
• Symptomatic, frequent high carbohydrate high protein diet

36. TYPE VII, TARUI DISEASE
• Cause: Phosphofructokinase (PFK) deficiency
• Covert fructose 6.phosphate to fructose 1,6 bisphosphate(key
regulator of glycolysis)
• 3 subunits
• M-muscle
• L-liver
• P-platlet

37. • Muscle contain M
• RBC contain M and L
• Clinical features-
• Exercise intolerance
• Hyperuricemia
• Abnormal polysaccharide in muscle
• Muscle weakness increase with carbohydrate rich meals
• Compensated haemolysis

38. • Rare types-
• Infantile-rapid myopathy Hypotonia and death by 4yrs
• Congenital-myopathy arthrogryposis and death
• Infant variant with developmental delay and seizures
• Adult-fixed muscle weakness
• Dx-demonstration of enzyme defect
• Rx-
• No specific treatment
• Ketogenic diet is promising

39. TYPE XI, FANCONI-BICKEL SYNDROME
• Hepatic glycogenosis with renal Fanconi syndrome
• Defect in GLUT-2
• Important in transporting glucose in and out of Hepatocytes,
Pancreatic B cells, intestine and basolateral membranes of renal
epithelial cells

40. • Clinical features-
• Present in 1st year
• Growth retardation
• Rickets
• Protuberant abdomen-hepatomegaly, nephromegaly
• Adults-
• Growth faltering causing short stature
• Excessive fat in abdomen
• Fracture( osteopenia)
• Malabsorption and diahrroea

41. • Fanconi like syndrome- Glycosuria, aminoaciduria,
phosphaturia
• Fasting hypoglycaemia
• Mild hypercholesterolemia
• Liver enzymes, uric acid and lactic acid remain normal
• Kidney
• Mesangial proliferation
• Microalbuminuria
• Glomerular hyperfilteration

42. • No specific treatments available
• Diabetic diet with small meals
• Correction of phosphate levels

43. TYPE IX GLYCOGEN STORAGE DISEASE
• Phosphorylase kinase deficiency
• Rate limiting step of glycogenolysis –phosphorylase enzyme
• Requires phosphorylase kinase
• 4 subunits expressed in different chromosomes

44. • Clinical features-
• Hepatomegaly
• Hyperketotic hypoglycaemia
• Hypotonia
• Gross motor development delay
• Hepatic fibrosis
• PCOS
• Renal tubular acidosis
• NO CARDIAC INVOLVEMENT, NO LACTIC ACIDOSIS
• Hepatic involvement, growth improve with age with normal
levels in adulthood

45. X LINKED PHOSPHORYLASE KINASE
DEFICIENCY
• Commonest glycogenoses
• Reduced enzyme activity in muscle liver RBC and fibroblasts
• Clinical features-
• Boys 1-5 years
• Growth retardation and Incidental finding of hepatomegaly

46. • Cholesterol triglycerides mildly elevated
• Liver enzymes mildly elevated
• Fasting hypoglycaemia with ketosis
• Uric and lactic acids remain normal
• Glucose response to glucagon is normal
• Hepatomegaly, blood chemical anomalies, growth improve with
age and normal values by adulthood
• Rarely can go in to cirrhosis

47. • Dx-
• Demonstration of enzyme activity reduction
• Mutation analysis
• Rx- is symptomatic
• High protein, high carbohydrate diet
• Corn starch/glucose

48. GLYCOGEN SYNTHASE DEFICIENCY
• Not essentially a GSD
• Early morning drowsiness, dizziness and convulsions
• No hepatomegaly
• No hyperlipidaemia
• Develop hyperglycaemia, glycosuria and increased lactate with
meals and glucagon

49. • Short stature
• Osteopenia
• Dx-
• Liver bx
• Demonstration of enzyme deficiency

50. •THANK YOU !!!