Glycogenosis type III (Cori-Forbes disease)

NeuroLearn NeuroHelp Muscle @

Background    Histopathology & Immunohistochemistry

BACKGROUND AND CLINICAL INFORMATION: Head  

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.

         Transferase: It takes the last three glucose residues beyond a branch point and transfers them to another branch.

         Glucosidase: removes the branching point residues.

         Abnormal glycogen: Although the morphology of the glycogen is normal under the electron microscope, their structure is abnormal on biochemical anaylsis.

Biochemical subtype:

         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.

Clinical manifestation:

         Mucle: Hypotonia 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.

         Hypoglycemia: There 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.

         Cardiomyopathy: Most 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: Head

Skin biopsy: Increased glycogen in eccrine clear cells.

Vascular smooth muscle: May contain glycogen storage.

Peripheral nerve: Glycogen storage has also been reported.

Muscle:

         General: Histological 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: Subsarcolemmal vacuoles up to 30 mm in size with many of them filled with PAD(+) material. Some vacules are clear and probably resulted from leakage.

EM: Extensive accumulation of morphologically normal glycogen particles in subsarcolemmal regions and in between fibrils. Small number of glycogen containing lysomal vacuoles may be present but are never as numerous as glycogenosis type II.