GLYCOGEN STORAGE

DISORDERSThese are a group of inherited disorders associated with glycogen metabolism, familial in incidence and characterized by deposition of normal or abnormal type and quantity of glycogen in the tissues

There are 6 classical types of glycogen

storage diseases

Type1)Von gierke’s disease

Type2)Pompe’s disease

Type3)Limit dextrinosis(Forbe’s disease)

Type4)Amylopectinosis(anderson’s disease)

Type5)McArdle’s disease

Type6)Her’s disease

TYPE 1:Von gierke’s disease

ENZYME DEFICIENCY :glucose-6-

phosphatase

INHERITANCE : Autosomal recessive

Liver cells and intestinal mucosal cells

are fully loaded with glycogen and

metabolically unavailable

CLINICAL AND BIOCHEMICAL FEATURES OF VON

GIERKE’S DISEASE

Only little amount of glucose is available is derived

from liver

So the children with this disease may tend to develop

hypogycemia

Fat is used as a energy source so it may lead to

LIPAEMIA,ACEDEMIA and KETOSIS

Excess of Acetyl coA is diverted for chosterol synthesis

this may lead to elevated level of cholestrol and

results in XANTHOMAS

Cont….

Increased fatty acid synthesis can produce fatty infiltration of liver

PERSISTENT HYPOGLYCAEMIA has 2 effects

Hypoglycemia inhibits insulin which in turn inhibits protein synthesis which results in DWARFISM

Hypoglycemia stimulates the secretion of CATECHOLAMINES which cause muscle glycogen to break down producing lactic acid and LACTIC ACIDOSIS

Increased blood lactic acid competes with urateexcretion by kidneys leading to increased blood uric acid levels

Children with increased uric acid synthesis may develop the symptoms of GOUT

PROGNOSIS

Children with this disease

may die young and some

of them survive till

adolescence

TYPE 2: POMPE’S DISEASE

ENZYME DEFICIENCY : ACID MALTASE enzyme which is present in lysosome and catalyses the

breakdown of oligosaccharides

INHERITANCE : AUTOSOMAL RECESSIVE

Here the glycogen structure is normal and the

organs which are involved is

HEART,LIVER,SMOOTH MUSCLE,AND STRAITED

MUSCLE

All the tissue contain excess of glycogen

CLINICAL FEATURES

Enlargement of heart (cardiomegaly)

Muscle weakness

PROGNOSIS

Infants usually die due to cardiac failure and broncho

pnuemonia

Death usually occurs before 9 months

TYPE 3 : LIMIT DEXTRINOSIS(FORBE’S

DISEASE)

ENZYME DEFICIENCY : DEBRANCHING ENZYME

INHERITANCE : AUTOSOMAL RECESSIVE

GLYCOGEN STRUCTURE : LIMIT DEXTRIN TYPE

Organs involved are heart liver and muscle

CLINICAL AND BIOCHEMICAL FEATURES

• HEPATOMEGALY

• MODERATE HYPOGLYCEMIA

• ACIDOSIS

• PROGRESSIVE MYOPATHY

• Enzyme deficiency can be

demonstrated in leucocytes

PROGNOSIS

Survives well to adultlife

TYPE 4 : AMYLOPECTINOSIS(ANDERSON’S

DISEASE)

ENZYME DEFICIENCY : BRANCHING ENZYME

INHERITANCE : NOT DEFINETELY KNOWN

Glycogen deposited is abnormal type, few

branch points and very long inner and outer

unbranched chains

LIVER is the mainly affected organ and other

organs are HEART, KIDNEY, and MUSCLES

Deposition is seen in RE SYSTEM

CLINICAL AND BIOCHEMICAL FEATURES

HEPATOMEGALY

SPLENOMEGALY

MODERATE HYPOGLYCEMIA

NODULAR CIRRHOSIS OF LIVER

HEPATIC FAILURE

Enzyme deficiency can be demonsrated in

leucocytes and liver

PROGNOSIS

Usually fatal

Longest survival is reported as 4 years

TYPE 5 : McArdle’s disease

ENZYME DEFICIENCY : MUSCLE PHOSPHORYLASE

INHERITANCE : AUTOSOMAL RECESSIVE

Glycogen deposited in normalstructure and the organs

involved are skeletal muscles

CLINICAL FEATURES

Muscle cramps on exercise

Pain

Stiffness and weakness of muscles

EPINEPHRINE TEST

After administration of epinephrine rise in

blood glucose occurs which shows that

hepatic phosphorylase activity is normal

TYPE 6 : Her’s disease

ENZYME DEFICIENCY : LIVER PHOSPHORYLASE

Glycogen deposited is normal in structure

Organs affected are mainly LIVERand LEUCOCYTES

CLINICAL AND BIOCHEMICAL FEATURES

HEPATOMEGALY

MODERATE HYPOGLYCEMIA

MILD ACIDOSIS