Glycogen storage disease with normal acid maltase: skeletal and cardiac muscles.

We report a 5-year-old boy with lysosomal glycogen storage disease and normal acid maltase activity. This patient, the fourth reported in the literature, was referred to our hospital for evaluation of elevated serum GOT, GPT, and CK activities. He had neither muscle weakness nor atrophy. Echocardiography demonstrated marked thickening of the intraventricular septum and left ventricular wall which indicated hypertrophic cardiomyopathy. Biopsied skeletal muscle disclosed massive accumulation of glycogen and autophagic vacuoles. Electron microscopy of biopsied cardiac muscle revealed severe myofibrillar disruption with marked accumulation of free and intralysosomal glycogen. Activities of all major glycolytic enzymes in skeletal muscle, including acid maltase, were normal. It is unknown why muscle lysosomes appeared to be unable to digest the trapped glycogen despite the presence of acid maltase. Our findings illustrate the importance of performing skeletal muscle investigation during childhood in patients with hypertrophic cardiomyopathy.

Skeletal muscle involvement in mucopolysaccharidosis type IIA: severe type of Hunter syndrome.

A patient with mucopolysaccharidosis type IIA (MPS IIA) and progressive gait disturbance is described. The histopathology of biopsied muscle was studied; Dorling's method revealed muscle fibers and interstitial cells containing metachromatic granules which suggested the storage of sulfated acidic glycosaminoglycans. Electron microscopy demonstrated that the membrane-bound vacuoles were present in muscle fibers, subsarcolemmal area, vascular endothelial cells, satellite cells, and endomysial fibroblasts. Besides clinical features, this ultrastructural pathology in MPS IIA muscles of MPS IIA was more severe than MPS IIB muscles. The accumulation of glycosaminoglycans in muscle tissue may be an additional factor contributing to gradual motor impairment of patients with MPS IIA.

Peripheral neuropathy in four cases of group A xeroderma pigmentosum.

We describe the clinical features and findings of biopsied sural nerves of 4 cases of xeroderma pigmentosum. Nine genetic forms of xeroderma pigmentosum have been reported by complementation studies. These four cases were diagnosed as Group A xeroderma pigmentosum by complementation studies using cultured skin fibroblasts. All cases had delayed mental and motor development in areas such as head control over 4 months of age and walking without support over 18 months of age. Three cases had the gradual onset of a gait disturbance between 6 and 9 years of age. Motor conduction velocity and sensory conduction velocity of the ulnar nerve were slightly delayed. The sural nerve of the slightly impaired patient showed a normal density of myelinated fibers, but a selective reduction of the large myelinated fibers with zebra-body-like structures in Schwann cell cytoplasm. The population density of all nerve fibers was severely diminished in the severely impaired cases. Ultrastructural observation disclosed many denervated Schwann cells and pockets of collagen isolated by loops of denervated Schwann cell cytoplasm. These findings suggest that the degenerative process in peripheral nerves of xeroderma pigmentosum is axonal. Peripheral neuropathy in Group A xeroderma pigmentosum resembles that of patients with ataxia telangiectasia who are known to have a defect in the repair mechanisms of their DNA in cultured skin fibroblasts.

Electron microscopic study of the biopsied cardiac muscle in Duchenne muscular dystrophy.

Cardiac muscular biopsies were performed on 4 patients with Duchenne muscular dystrophy (DMD). None of the patients had cardiac symptoms and all of them exhibited normal electro- and echocardiographic findings. Electron microscopic examination of cardiac muscles from 4 patients with DMD disclosed proliferation of the mitochondria, changes in the cristae, abnormalities of the Z-bands, dilatation of the sarcoplasmic reticulum, deposition of glycogen, and changes in the nuclei. The most striking finding in these patients was that the residual bodies were increased and were observed mainly in the perinuclear region. These ultrastructural features suggest that an extreme exhaustion had already been present in myocardial tissue of the patients prior to the onset of cardiac symptoms.