Department of Pathology, University of Oklahoma Health Sciences Center

NeuroTest Question #79 NeuroLearn   NeuroHelp Next question Previous question

Answer: McArdle’s disease (myophosphorylase deficiency).  Level of difficulty: 3 NeuroTest NeuroLearn NeuroHelp

Pathology of this case: 

• There is an accumulation of an amorphous, granular, non-membrane bound osmophilic substance in between myofibrils in the form of irregular collections. These amorphous substance is most compatible with glycogen. There are some mitochondria and some fat droplets. This electron micrograph is taken from a case of McArdle's disease. [Click here to see a case of McArdle's disease]

Differential diagnosis:

• Mucopolysaccharides: Mucopolysaccharidoses are characterized by abnormal lysosomal accumulation of mucopolysaccharides or glycosaminoglcan resulted from deficiency of a lysosomal glucosidase or sulfatase. Common to all mucosaccharidoses are dysmorphic changes and excretion of mucopolysaccharides in urine. The CNS is affected to different extents in different subtypes and only type IH and III have severe effects on the CNS. Common to all types of mucopolysaccharidoses is abnormal lysosomal storage of mucopolysaccharides. Histologically, mucopolysaccharides are highly water-soluble and cannote be demonstrated on routine sections. Under the electron microscope, there may be large membrane-bound, largely empty vacuoles that sometimes contain lamellae. Neuronal storage can occur and the storage material essentially has features of primary gangliosidosis. Some of them appear concentric, tightly packed lamellae while others contain loosely arranged, parallel arrays of lamellae giving rise to the so-called zebra bodies. Although zebra bodies are regarded as a typical finding in mucopolysaccharides, they are also seen in other storage diseases.
• Fabry’s disease (a-galactosidase deficiency): Fabry’s disease is an X-linked lysosomal storage disease due to a-galactosidase A deficiency that leads to the accumulation of ceramide trihexoside and ceramide dihexoside. Major clinical manifestations include telangiectases, burning pain in the limbs and abdomen, unexplained fever and autonomic dysfunction. Pathologically, it is essentially a vasculopathy with ballooning of endothelial cells accompanied by deposit of lipid in endothelial cells, a process that lead to thromboses. As a result, hypertension, myocardial infarction, and strokes are common among these patients. Death is often due to renal involvement.  Muscle fibers and wall of intramuscular vessels contain punctuate acid phosphate-positive activity that reflects the lysosomal nature of the storage.. Lamellar material with a periodicity of 5.5 nm are seen under electron microscope.
• Duchenne's muscular dystrophy is not associated with abnormal cytoplasmic storage.
• Central core disease: This is the first congenital myopathy being recognized. Central core disease is most often seen in children but can also become symptomatic in adults. Some of them remain asymptomatic. Most of the cases are transmitted in an autosomal dominant fashion, some putative autosomal recessive cases have been reported. Mutations in the gene for the ryanodine receptor (RYR1) on chromosome 19q have been found in some patients with central core disease; all appear to be missense mutation. Patients are susceptible to develop malignant hyperthermia. The pathologic hallmark is a centrally located core in a muscle fiber that is composed of disorganized myofibrils. Histochemically, the core does not contain oxidative enzymes and appears as pale areas on NADH-TR, SDH and cytochrome C oxidase preparations. Under the electron micrscope, the cores are disorganized fibrils. [Click here to see a case of central core disease]

Comment: KarMing-Fung@ouhsc.edu