Glycogenosis type III (Cori-Forbes disease)
Background Histopathology & Immunohistochemistry
BACKGROUND AND CLINICAL INFORMATION:
Summary of glycogenosis Classificaiton of glycogenoses by enzyme deficiency
Summary: Glycogenosis type III is resulted from deficiency of the debranching enzyme amylo-1,6-glucosidase. It involves muscle, liver, heart, and rarely peripheral nerve. There is hypoglycemia and sometimes chronic hyperuricemia. The clinical manifestations are mild and therefore glycogenosis type III is compatible with long term survival and close to normal daily life.
Genetics: The gene is on chromosome 1p21; the
pattern of inheritance is autosomal recessive.
Biochemistry: The enzyme has two separate catalytic subunits.
It takes the last three glucose residues beyond a branch point and transfers
them to another branch.
removes the branching point residues.
Although the morphology of the glycogen is normal under the electron microscope,
their structure is abnormal on biochemical anaylsis.
Type A: Lacks
enzymatic activity and immunoreactivity for the enzyme in both liver and muscle.
Type B: Lacks
enzymatic activity and immunoreactivity for the enzyme in only the liver. This
type has no muscular or cardiac manifestation.
Type C: The
transferase activity is deficient in both liver and muscle but immunoreactivity
for the enzyme is normal. Clinically, they are similar to type A.
Definitive diagnosis: Demonstration of enzyme deficiency in muscle or
liver biopsy or leukocytes.
and weakness. The manifestations may, althoughn uncommon, begin at birth.
Muscular symptoms are more common in the second or third decade. The myopathy in
some patients is static. Progressive myopathy also occurs.
is fasting hypoglycemia and limited fasting intolerance. Due to the lack of
glucose supply, the lactate level does not rise on exercise.
Chronic hyperuricemia is
seen in some cases.
Liver function: Most
patients have early signs of liver disease in children with hepatomegaly.
cases with myopathy may have abnormal EKG and echocardiographic findings.
Cardiac insufficiency is present in only about 20% of patients.
Peripheral nerve: Only
rarely affected and have slow conduction velocity.
CK may be
normal or elevated.
HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY:
Skin biopsy: Increased glycogen in eccrine clear cells.
Vascular smooth muscle: May contain glycogen storage.
Peripheral nerve: Glycogen storage has also been reported.
appearance may be quite normal in many cases.
Fiber types: Both
types are affected and scattered atrophic fibers of both types are often seen.
vacuoles up to 30 mm in
size with many of them filled with PAD(+) material. Some vacules are clear and
probably resulted from leakage.