GLYCOGEN STORAGE DISEASES (GSDs)

2.  The metabolic defects concerned with the
glycogen synthesis and degradation are
collectively referred to as glycogen storage
diseases.
 These disorders are due to defects in the
enzymes.
 The inherited disorders are characterized by
deposition of normal or abnormal type of
glycogen in one or more tissues.

3.  It is transmitted by autosomal recessive trait.
 Enzyme deficiency: Glucose 6-phosphatase.
 The enzyme is absent in liver cells & intestinal
mucosa.
 Liver cells, intestinal mucosa & renal tubular
epithelial cells are loaded with glycogen,
which is normal in structure but metabolically
not available.

4.  Fasting hypoglycemia:
 Hypoglycemia, decreases insulin secretion,
which in turn inhibits protein synthesis
causes stunted growth (dwarfism).
 Lactic acidemia:
 Glucose is not synthesized from lactate
produced in muscle & liver.

5.  Lactate level in blood increases & the pH is
lowered (acidosis).
 Hyperlipidemia:
 Fat is utilized as energy source, which leads
to lipaemia, acidaemia & ketosis.
 Excess of acetyl CoA resulting in increased
cholesterol levels, produce xanthomas.
 There is a blockade in gluconeogenesis.

6.  Hyperuricemia:
 Glucose 6-phosphate that accumulates is
diverted to HMP Shunt, leading to increased
synthesis of ribose phosphates which increase
the cellular levels of phosphoribosyl
pyrophosphate & enhance the metabolism of
purine nucleotides to uric acid (gouty arthritis).

7.  Enzyme deficiency: Lysosomal α-1,4
glucosidase (acid maltase).
 Glycogen accumulates in lysosomes in all
most all the tissues.
 Enlargement of heart (cardiomegaly).
 Nervous system is also affected.
 No hypoglycemia
 Death occurs due to heart failure.

8.  Enzyme deficiency: Amylo a-1,6-glucosidase
(debranching enzyme)
 Organs affected - Liver (Hepatomegaly),
muscle, Heart, leucocytes
 Branched chain glycogen accumulates.
 Clinical manifestations are similar to von
Gierke's disease but glycogen is abnormal.
 Moderate hypoglycemia.

9.  Enzyme deficiency:
 Glucosyl 4-6 transferase (branching enzyme)
 Glycogen deposited is abnormal.
 Glycogen with only few branches accumulate.
 Organs mainly affected - liver
(Hepatomegaly), heart, muscle & kidney.
 Moderate hypoglycemia, ascites, cirrhosis of
liver & hepatic failure & usually fetal.

10.  Enzyme deficiency:
 Muscle glycogen phosphorylase
 Glycogen deposited is normal in structure.
 Organs involved - skeletal muscle.
 Muscle cramps on exercise, pain, weakness &
stiffness of muscles.
 No lactate is formed.
 Muscle may get damaged.

11.  Enzyme deficiency:
 Liver glycogen phosphorylase.
 Glycogen deposited is normal in structure.
 Organs mainly affected liver.
 Hepatomegaly, moderate hypoglycemia, mild
acidosis, liver glycogen cannot form glucose
(pyruvate & lactate can be precursors for
glucose).

12.  Enzyme deficiency: Phosphofructokinase
 Organs affected - skeletal muscles.
 Accumulation of glycogen in skeletal
muscles.
 Glucose 6-phosphate & fructose 6-phosphate
is also accumulated.
 Muscle cramps.

13.  Enzyme deficiency:
 Hepatic phosphorylase kinase.
 Failure of hepatic glycogen phosphorylase
activity leading to decrease in glycogenolysis.
 Hepatomegaly, mild to moderate
hypoglycemia.

14.  Textbook of Biochemistry-MN Chatterjea
 Textbook of Biochemistry-U Sataynarayana
 Textbook of Biochemistry-DM Vasudevan