Glycogen storage

diseases

Dr.M.Ganesan
First year post graduate
Dept of biochemistry
Gmkmc
salem
Genetic diseases –caused be defects
in enzymes of glycogen
degradation

rarely-glycogen synthesis
COURTESY:TEXTBOOK OF BIOCHEMISTRY VASUDEVAN
 Glycogen Storage Diseases

-- These enzymes normally catalyze

reactions that ultimately convert glycogen to
glucose or glucose-6 phosphate

•Enzyme deficiency results in glycogen

accumulation in tissues.
 symptoms
• Liver-hypoglycemia

• Muscle-weakness,exercise intolerance
 Type 0
• Enzyme defect:Glycogen synthase

• Features:
Hypoglycemia; hyperketonemia; early
death
 Type I:glucose-6-phosphatase deficiency
• Enzyme defect: Glucose-6-phosphatase

• Incidence: 1 in 100000 live births

• Organ involved: Liver

• Features:
• Glycogen accumulation in liver and renal tubule cells
• Enlarged liver
• hypoglycemia
• lactic acidemia
• ketosis
• Hyperlipidemia
Courtesy:Atlas of metabolic diseases,Nyhan bruce
 diagnosis
• Galactose load test
• Epinephrine tolerance test
• Glucose -6-phosphatase assay
• Type 1a-von Gierke disease-defect in catalytic
sub unit

• Type 1b-defect in transport system

• Type1c-defect in microsomal transport

 Treatment
• Frequent meals
• Nasogastric feeding at the night
 Type II: Pompe’s disease
Enzyme defect: Lysosomal α-1,4 glucosidase
(acid maltase)

Organs involved: All organs( heart,muscle)

• Features: Glycogen accumulation in lysosomes
• Infantile onset (pompe disease): muscle
hypotonia, death from cardiac failure by age 2

• Juvenile form present in second or third

decade of life. milder form
• Treatment:myzozyme(recombinant enzyme)
Courtesy:Atlas of metabolic diseases,Nyhan bruce
Courtesy:Atlas of metabolic diseases,Nyhan bruce
Type III: Cori’s disease or limit dextrinosis

• Enzyme defect: Amylo α-1,6 glucosidase

(debranching enzyme)

• Organs involved: liver, muscle. heart, leukocytes

• Features: Accumulation of branched chain

glycogen; liver enlarged; hypoglycemia; muscle
weakness.
• Clinical features-resembles type 1

• Differentiated by
• Galactose load
• Low uric acid and lactate
• Increased serum transaminase and creatine
kinase
 Type IV: Andersen’s disease or
amylopectinosis

Enzyme defect: Glucosyl 4-6 transferase

(branching enzyme)

Organs involved: Most tissues

Features: Hepatosplenomegaly
liver cirrhosis,accumulation of glycogen with
few branches
COURTESY:HARPER TEXTBOOK OF BIOCHEMISTRY
Courtesy:Atlas of metabolic diseases,Nyhan bruce
• Enzyme deficiency is demonstrated in
leukocytes and cultured fibroblasts
 Type V: McArdle’s disease

Enzyme defect: Muscle glycogen phosphorylase

Organs involved: Skeletal muscle

Features: usually in second or third decade of life.

moderate exercise can be sustained
• Second wind phenomenon

• Increased plasma creatine kinase and

myoglobinuria
 Type VI: Her’s disease

• Enzyme defect: Liver glycogen phosphorylase

• Organs involved: Liver

• Features: Hepatomegaly; accumulation of glycogen

in liver; mild hypoglycemia; ketosis.

• Enzyme activity in liver ,RBC,WBC

 Type VII: Tauri’s disease

Enzyme defect: Muscle and erythrocyte

phosphofructokinase

Organs involved: Skeletal muscle, erythrocyte

Features: Muscle cramps due to exercise,

hemolytic anemia; poor exercise tolerance.
• Phosphofructokinase catalyzes the rate-
limiting step in glycolysis.

• Phosphofructokinase deficiency leads to

muscle pain and exercise-induced fatigue and
weakness.
 Type VIII
• Liver phosphorylase kinase

• Mild hypoglycemia
 Type IX
• Enzyme muscle phosphorylase kinase

• Clinical features that of type VI

 Type x
• Enzyme defect:cAMP dependent protein
kinase A

• Hepatomegaly ,accumulation of glycogen in

liver
Type Name Enzyme Clinical Features
Deficiency
0 — Glycogen Hypoglycemia;
synthase hyperketonemia; early death

I Von Glucose 6- Glycogen accumulation in liver

Gierke's phosphata and renal tubule cells;
disease se hypoglycemia; lactic acidemia;
ketosis; hyperlipemia
II Pompe's 6 Accumulation of glycogen in
disease glucosidas lysosomes: juvenile onset
e (acid variant, muscle hypotonia,
maltase) death from heart failure by age
2; adult onset variant, muscle
dystrophy
Type Name Enzyme Clinical Features
Deficienc
y
III Limit Debranch Fasting hypoglycemia;
dextrinosis, ing enzy hepatomegaly in infancy;
Cori's me accumulation of characteristic
disease branched polysaccharide
IV Amylopectin Branching Hepatosplenomegaly;
osis, enzyme accumulation of polysaccharide
Andersen's with few branch points; death
disease from heart or liver failure in first
year of life
V Myophospho Muscle Poor exercise tolerance; muscle
rylase phosphor glycogen abnormally high (2.5–
deficiency, ylase 4%); blood lactate very low after
McArdle's exercise
syndrome
Type Name Enzyme Clinical Features
Deficienc
y
VI Hers' Liver Hepatomegaly; accumulation of
disease phosphor glycogen in liver; mild
ylase hypoglycemia; generally good
prognosis
VII Tarui's Muscle Poor exercise tolerance; muscle
disease and RBC glycogen abnormally high (2.5–
PFK 1 4%); blood lactate very low after
exercise; also hemolytic anemia
VIII Liver Hepatomegaly; accumulation of
phosphor glycogen in liver; mild
ylase hypoglycemia; generally good
kinase prognosis
Type Name Enzyme Clinical Features
Deficienc
y
IX Liver and Hepatomegaly; accumulation of
muscle glycogen in liver and muscle;
phosphor mild hypoglycemia; generally
ylase good prognosis
kinase
X cAMP- Hepatomegaly; accumulation of
dependen glycogen in liver
t protein
kinase A
 References
• TEXTBOOK OF BIOCHEMISTRY
D.M.VASUDEVAN

• HARPER TEXTBOOK OF BIOCHEMISTRY

• LIPPINCOTT BIOCHEMISTRY
• ATLAS OF METABOLIC DISEASES NYAN BRUCE
Thank you