Transcript GSD - imtech

Glycogen Storage Diseases
Type 0
Type IV
Type III
Type I
Type VII
Excess glucose
Storage
Glycogen granules -- complex aggregates of
glycogen and the enzymes that synthesize it
and degrade it, and the machinery for
regulating these enzymes.
Glycogen
Starch
Vertebrates
Microorganisms
Plants
Glycogenin
(glucosyltransferase
activity)
5
6
Glycogenin (chain
extending activity)
Glycogen synthase
Glycogen branching
enzyme
4
Glucose 6phosphate
Glucose 6phosphatase
1
3
Type І GSD (von Gierkes disease):----- The most common and severe form of glycogen storage disease.
Patients with Type І GSD are unable to release glucose from glycogen due to the deficiency of glucose-6phosphatase and hence with time glycogen builds up in the liver.
----- Characterized by massive enlargement of liver (hepatomegaly), growth retardation, fasting hypoglycemia,
increased lactic acid concentrations in the blood (due to excessive glycolysis), hyperuricemia and
hypertriglyceridemia.
----- Treatment consists of providing frequent meals and naso-gastric feeding at night to maintain blood
glucose concentration.
Type Іb ----- has been identified as a defect in the glucose–6–phosphatase transport system.
----These patients in addition to the problems described above develop frequent bacterial and fungal infection,
due to abnormal functioning of the white blood cells.
Type II
Type II GSD affects predominantly the heart and skeletal muscle producing muscle weakness and
cardiomegaly. Liver function is normal and patients do not have hypoglycemia.
----- caused by a lack of function of the enzyme acid glucosidase, which is present in lysosomes. Without
the proper functioning of this enzyme, the glycogen that comes into the lysosomes is not broken down, but
accumulates and disrupts the normal functions of the cell. In muscle tissue, these enlarged lysosomes
eventually cause the cells to become dysfunctional and die. There are mainly two forms of Type II GSD.
------ Infantile form (Pompe’s disease): This appears in the first few months of life with weakness and
respiratory difficulties. The patients usually die before 12 months of age due to cardiac failure and respiratory
weakness.
Juvenile forms: A milder form and may present in the second or third decade of life with muscle weakness
and difficulty in walking.
------ Treatment of aimed at relieving stress on the muscles. A protein-rich diet is used, along with an intensive
daily exercise program.
Type III
Deficiency of Amylo-1, 6–Glucosidase the debranching enzyme results in storage of an abnormal form of
glycogen.
Two subtypes of this disorder IIIa & IIIb have been observed. In GSD Type IIIa, the disease involves both liver
and muscle tissues, producing hepatomegaly and muscle weakness. Type IIIb involves only the liver without
apparent muscle disease.
Clinical and biochemical features resemble those of type І disease. Differentiation from type І is by a lower
concentrations of urate and lactate in the blood and elevated serum transaminase and creatinine kinase
activities.
Treatment of Type III GSD consists of frequent feedings and a high protein diet. Continuous nasogostric
feedings similar to those used for Type І GSD are useful.
Type V
In the absence of phosphorylase in muscles, glucose cannot be released from the glycogen stored in
skeletal muscles for energy. Hence people with Type V GSD, also called McArdle disease, experience
problems performing and completing most exercises. These patients experience muscle pain, muscle cramps,
muscle fatigue and muscle tenderness. With the breakdown of muscle and the release of myoglobin,
myoglobinuria may develop.
These patients should exercise moderately, for extensive exercise can cause considerable muscle breakdown
resulting in great deal of release of myoglobin in the urine. However, patients with type V GSD respond to oral
glucose administration.
Type VI
Type VI GSD also known as Hers’ disease is a rare and relatively benign disorder due to the deficiency of
liver phosphorylase or one of the subunits of phosphorylase kinase.
Enlargement of liver due to increased deposit of glycogen, growth retardation and mild hypoglycemia are
seen.
Type VII
Patients with Type VII GSD also known as Tarui’s disease have deposits of abnormal glycogen in
muscle. With the deficiency of phosphofructokinase, effective glycogen breakdown (glycolysis) during
muscle stress cannot be accomplished, resulting in pain, weakness, and cramping in the exercising
muscle.
Exercise intolerance, unresponsiveness of glucose administration and decreased glycolysis in
erythrocytes produces myoglobinuria, hyperbilirubinemia and reticulocytosis.