Kimio Sasaki

Muscle pathology in Marinesco-Sjogren syndrome: a unique ultrastructural feature.

The light- and electron-microscopical findings in the skeletal muscle of a patient with Marinesco-Sjogren syndrome (MSS) are presented. Muscle biopsy specimens showed myopathy with slightly dystrophic changes including variation in fiber size, muscle fiber necrosis, regeneration and rimmed vacuole formation. Fiber type analysis with myosin ATPase staining showed a mild increase in type 2C fibers. Electron microscopy revealed autophagic vacuoles with numerous myeloid bodies, and a unique dense membranous structure associated with nuclei. We consider that this unique membranous structure is an important feature in the muscle pathology of MSS.

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.

Tomaculous neuropathy in Charcot-Marie-Tooth disease with myelin protein zero gene mutation

Mutation of the myelin protein zero (MPZ) gene is associated with a small number of Charcot-Marie-Tooth (CMT) patients. We present a patient with Lys 130 Arg substitution in the extracellular domain who showed tomacula formation in biopsied sural nerve. CMT patients with mutations Ly 96 Glu, Lys 130 Arg and Ile 135 Leu showed tomaculous neuropathy. Present and previously reported investigations suggest that the pathological phenotypes of peripheral nerve are probably related to the mutations of the MPZ gene.

Demyelinating peripheral neuropathy in cockayne syndrome: a histopathologic and morphometric study

The clinical and histopathological features of Cockayne syndrome in a 2-year-old girl are reported. Sural nerve biopsy revealed segmental demyelination and remyelination. The density of myelinated fibers, especially small ones, was decreased in comparison with an age-matched control. Although the total number of unmyelinated fibers showed no difference from that in the control, the number of small unmyelinated fibers was slightly increased. A study of teased fibers from the patients nerve revealed that 1% of the fibers had segmental demyelination, and 7% showed remyelination. Ultrastructurally, demyelinated fibers were present sporadically. No degeneration of axons was evident. Our pathological and morphometric data for the sural nerve suggest the presence of primary demyelination in early childhood.

A new mutation of the Po gene in patients with Charcot-Marie-Tooth disease type 1B: screening of the Po gene by heteroduplex analysis

Most of Charcot-Marie-Tooth (CMT) 1 families are associated with a duplication in chromosome 17p11.2-p12, which includes the gene encoding peripheral myelin protein-22 (PMP-22). Point mutations of the Po gene have been identified in a few of the CMT 1 families in whom no duplication was found. We investigated a new mutation of the Po gene in one of those families. A to G substitution of nucleotide 389 in exon 3 resulted in Lys 131 Arg substitution. This structural change of extracellular domain of Po would alter the function of Po and result in an impairment of peripheral myelin compaction.

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. (J Child Neurol 1988;3:114-119).

Early-onset benign autosomal-dominant limb-girdle myopathy with contractures (Bethlem myopathy).

We report the first Japanese patients, a mother and son, with early-onset, benign, autosomal-dominant, limb-girdle myopathy with contractures (Bethlem myopathy). The clinical features revealed predominantly proximal muscle weakness--especially in the limb-girdle muscles--joint contractures increasing with age, a benign course, and the absence of cardiac involvement. Muscle histology revealed nonspecific myopathy changes without dystrophic features. Electromyogram revealed a reduced interference pattern with a giant spike suggesting a neurogenic process.

Walker-Warburg syndrome in a Japanese patient

We report the first Japanese female patient with Walker-Warburg syndrome. She had generalized muscle hypotonia with hydrocephalus due to Dandy-Walker malformation and bilateral microphthalmia with opaque corneas. She had severe motor and mental retardation. Muscle histology reflected advanced changes of muscular dystrophy. We discuss the relationship between Fukuyama congenital muscular dystrophy and Walker-Warburg syndrome, both of which fall within a spectrum of developmental abnormalities with a common cause. In Fukuyama congenital muscular dystrophy, ocular abnormalities are less severe.

Congenital muscular dystrophy with partial deficiency of merosin

We present a Japanese patient who has congenital muscular dystrophy, with partial merosin deficiency. The patient had characteristic findings of clinical features and brain MRI. Muscle biopsy showed advanced muscular dystrophy, with greatly reduced muscle fibers and massive infiltration of interstitial connective and fatty tissues. On immunostaining for cytoskeletal proteins, merosin was greatly reduced. The other cytoskeletal proteins, including dystrophin and 50 kDa alpha-sarcoglycan were normally expressed around all muscle fibers.

Mosaic pattern of dystrophins in Duchenne muscular dystrophy.

Dystrophin is the gene product affected in Duchenne muscular dystrophy (DMD). Dystrophin is demonstrably absent with immunocytochemical staining and undetectable by western blotting of DMD muscles. We report an isolated 7-year-old girl with DMD. Analysis of the patients and her mothers DNA, with probes covering the DMD gene, disclosed no deletion. We have studied dystrophin in biopsied muscle from the patient using antidystrophin antibody in combination with immunofluorescence. Random presence of normal and dystrophin-deficient fibers were indicative of mosaic expression. Dystrophin immunocytochemistry may be useful for accurate diagnosis of affected females.