1. GLYCOGEN
STORAGE
DISEASE
ROTO ROBO
INTERNAL MEDICINE

2. INTRODUCTION
These are group of inherited inborn errors of
metabolism due to deficiency or dysfunction of
enzymes related to glycogen metabolism.
Usually manifestations are confined to liver and
muscle but some cause more generalized
pathology and affect tissues such as the
kidney, heart and bowel.

3. GLYCOGEN
Glycogen is the storage polysaccharide and is
sometimes called animal starch.
It is highly branched structure with chains of
12–14 α-D-glucopyranose residues.
Most of the glucose residues in glycogen are linked
by α-1-4-glycosidic bonds.
Branches at about every 4th to 10th residue are
created by α-1,6-glycosidic bonds.
The chains are arranged in concentric layers.

4. STRUCTURE OF GLYCOGEN

5. GLYCOGEN METABOLISM

6. GLYCOGENESIS

7. GLYCOGENOLYSIS

9. GLYCOGEN STORAGE DISORDERS (GSD)
• Glycogen storage disease is a generic term to describe
group of inherited disorders characterized by deposition of
an abnormal type or quantity of glycogen in tissues, or
failure to mobilize glycogen.
• GSD were categorized numerically in the order in which
enzymatic defects were identified.
• They are also classified by the organs involved & clinical
manifestations.
• Overall incidence is estimated at 1 / 20,000 live births.
• Inheritance patterns
- Autosomal recessive (I, II, III, IV, V, VII, some IX).
- X-linked (some IX, VI)

11. LIVER GLYCOGEN STORAGE DISEASE
Ia / Von Gierke Glucose-6-phosphatase Common,
Severe hypoglycemia, hepatic
adenomas & ca, renal failure
Ib Glucose-6-phosphate ~10% of type I
translocase
IIIa / cori or forbes Liver & muscle debranching Common, mild hypoglycemia, hepatic
enzyme adenoma & carcinoma
IIIb Liver debranching enzyme ~15% of type III
VI /Hers Liver phosphorylase Rare , often benign
IX Liver phosphorylase kinase Common, x-linked,
0 Glycogen synthase Decreased glycogen store
XI / Fanconi-Bickel Glucose transporter-2 Rare ,consanguinity in 70%
DISORDER WITH LIVER CIRRHOSIS
IV / Andersen Branching enzyme One of rarer glycogenoses

12. MUSCLE GLYCOGEN STORAGE DISEASE
V / McArdle Muscle phosphorylase Common, male
predominance
VII / Tarui phosphofructokinase Ashkenazijews & japanese
Phosphoglycerate kinase deficiency Rare , x-linked
Phosphoglycerate mutase deficiency Rare , african , american
Lactate dehydrogenase Lactic acid Rare
dehydrogenase
Fructose 1,6-bisphosphate aldose A deficiency Rare
Pyruvate kinase deficiency muscle isozyme Rare
Muscle phosphorylase kinase deficiency Rare , autosomal recessive
B-enolase deficiency Muscle b-enolase rare

13. GLYCOGEN STORAGE DISEASE CAUSING SKELETAL
MYOPATHY AND / OR CARDIOMYOPATHY
II / Pompe Lysosomal acid Common, undetectable, or
a-glucosidase very low level of enzyme
activity on infantile form
Cardiac phosphorylase kinase deficiency Severe cardiomyopathy &
early heart failure,
Very rare

14. TYPE I, VON GIERKE'S DISEASE
 Itis the most common GSD
Affected enzyme: glucose-6-phosphatase
Affected tissue: Liver, kidney and intestinal mucosa
Two subtypes-
1. Type I a- glucose-6-phosphatase enzyme is
defective
2. Type I b- glucose-6-phosphatase translocase is
defective

15.  Clinical features:
 Neonatal period - Hypoglycemia & lactic acidosis
Hepatomegaly by 3-4 months of age
Easy bruising & epistaxis d/t prolonged bleeding
time.
Kidneys - enlarged, but normal spleen & heart size
Hyperuricemia and hyperlipidemia.
Type I b - neutropenia with reccurrent infection,
oral & mucosal ulceration.

16. Long term complications
 Puberty delayed
 Gout becomes symptomatic by puberty.
 Increased bleeding during menstrual cycles- life threatening
menorrhagia
 2nd & 3rd decade - hepatic adenoma > haemorrhage >
malignant.
 Renal - proteinuria, Hypertension, stones, altered
creatinine, complete failure.

17. TYPE II, POMPE'S DISEASE
 Affected enzyme- α-1,4-glucosidase (acid maltase)
Clinical feature: Clinical spectrum is continuous &
broad, with presentation in infants, children and adults.
1. Infantile Form
 Infant normal at birth, develop generalised muscle
weakness with feeding
difficulties, Hepatomegaly, cardiomegaly, CHF due to
HCMP death before 1 yr of age
2. Juvenile form
 Delayed motor milestones & difficulty in walking
 Swallowing difficulties , proximal Ms weakness &
respiratory Ms involvement & death before end of 2nd

18. 3. Adult form
 Slowly progressive myopathy
without overt cardiac
involvement.
 Onset between 2nd & 7th
decade
 Dominated by progressive
muscle weakness with truncal
involvement.
 Pelvic girdle, paraspinal Ms
& diaphragm are seriously
affected.

19. TYPE III, CORI OR FORBES DISEASE
Affected enzyme: Glycogen debranching enzyme
Affected tissues: Liver and muscle
Subtypes:
1. type III a - Both liver & muscle involved
2. type III b – Only liver involved (15%)
Clinical features:
 Hepatomegaly, hypoglycemia, short
stature, variable skeletal myopathy and
cardiomyopathy.
 Hyperlipidemia, elevated liver transaminases.
 Hepatomegaly improves with age.
 Liver cirrhosis & hepatocellular carcinoma may
occur in late adulthood.

20. TYPE IV, ANDERSEN'S
DISEASE, AMYLOPECTINOSIS
Affected enzyme: Glycogen branching enzyme
Affected tissues: Liver
Clinical features:
– Hepatomegaly, failure to
thrive, cirrhosis, splenomegaly, jaundice, hypotonia,
waddling gait, lumbar lordosis.
Treatment: Liver transplant.
Prognosis: Mostly death within 4 yr of age due to
cirrhosis and portal hypertension.

21. TYPE V, MCARDLE'S DISEASE
 Affected enzyme: Muscle phosphorylase deficiency
 Affected tissue: Muscle
 Clinical features
 Symptoms develop in adulthood with exercise
intolerance & muscle cramps
 Two types of activity –
1 .Brief exercise of great intensity
2. Less intensity but sustained activity
 35% report permanent pain that seriously affects sleep
& other activities.
 Half of pt report burgundry-coloured urine after
exercise, resulting from myoglobinuria 20 to
rhabdomyolysis, which later can lead to renal failure.

22. TYPE VI, HERS DISEASE
 Affected enzyme: Liver phosphorylase
 Affected tissues: Liver, rare cardiac form
 Clinical features:
Most common variant is X-linked
Hepatomegaly, hypoglycemia, growth
retardation, hyperlipidemia.
Treatment: Cardiac transplantation for rare cardiac form
Prognosis: Usually normal life span.

23. TYPE VII, TARUI DISEASE
 Affected enzyme: Phosphofructokinase(PFK)
Affected tissue: Muscle
Clinical features:
Exercise intolerance, muscle cramping, exertional
myopathy, compensated haemolysis &
myoglobinuria.
Note : Symptoms can be similar to McArdle's
Glycogen Storage Disease but more severe.

24. TYPE IX, GLYCOGEN STORAGE DISEASE
 Affected enzyme: liver phosphorylase kinase deficiency
 Different subtypes –
Gene/subunit involved, Tissue affected, Mode of inheritance
 Clinical features
 Child 1-5 yr age – growth retardation, hepatomegaly
 Cholesterol, triglycerides & liver enzymes mildly elevated.
 Fasting ketosis, mild hypoglycemia.
 Most adult reach normal final Ht & practically asymptomatic
 Prognosis is good, hepatomegaly & abnormal blood chemistries
return to normal with age.

25. TYPE 0, LEWIS DISEASE
Affected enzyme: Hepatic glycogen synthase.
Affected tissues: Liver.
Clinical features
Seizures can occur.
Fatigue and muscle cramps after exertion.
Mild growth retardation in some cases.

26. INVESTIGATION
 Blood tests:
– Blood glucose: hypoglycemia is likely
– Liver function tests: monitoring for hepatic failure
– Anion gap calculation: may indicate lactic acidaemia
– Urate
– Creatinine clearance
 Urine tests:
 Myoglobinuria after exercise found in 50% of people with
McArdle's disease.

27. INVESTIGATION
 Imaging
USG abdomen - hepatomegaly
Echocardiography - to look for cardiac
involvement in certain types of GSD
 Biopsy
Of liver.
Muscle or other tissues gives definitive
diagnosis.

28. DIAGNOSIS
 Clinical presentation
 Abnormal biochemical parameters
 Liver & muscle biopsy for enzyme deficient.
 Gene based mutation analysis.
prenatal diagnosis:
 chorionic villus sampling and
amniocentesis can be used to determine
enzyme activity in a fetus.

29. TREATMENT
 Supportive treatment
 maintaining normal blood sugar level
 Supplementation of multivitamins, calcium & vit D
Allopurinol - raised uric acid.
 ACE-inhibitors - microalbuminuria.
 Statin - hyperlipidemia
 Diet therapy : high-protein, low-carbohydrate diet
 Physiotherapy and occupational therapy may be
required

30. TREATMENT
 Enzyme replacement therapy – Pompe disease
Alglucosidase alfa (Myozyme) recombinant human
acid alpha - glucosidase at 20 mg/kg every 2 weeks
 Genetic counselling
Gene therapy remains a potentially effective
treatment for the future.

31. THANK YOU
THANK YOU….