Neuroradiological findings in glutaric aciduria type I: report of four Japanese patients.

We examined neuroradiological computerized tomography (CT) findings and the clinical course of four Japanese children with glutaric aciduria type I (GA1) whose enzyme activity of glutaryl-CoA dehydrogenase was undetectable. Brain CT in all cases examined showed low density white matter, fluid collection in bilateral frontotemporal regions (particularly surrounding the Sylvian fissures), enlargement of the lateral ventricles and slight atrophy of the basal ganglia. Although these findings seemed to be characteristic for GA1, they were unlikely to be more extended, at least over 2 years after infancy. The low density white matter was observed more evidently in the neonatal or early infantile periods than in later periods. The degree of enlargement of fissures in bilateral frontotemporal regions about the Sylvian fissures appeared to correlate with the severity of symptoms such as dystonia or choreoathetosis. Magnetic resonance images (MRI) in one case showed bilateral linear-shaped low intensity in areas of the external capsules and putamen on a T1-weighted image. These CT and MRI findings, as well as clinical symptoms such as choreoathetosis or dystonia, may suggest that metabolic abnormalities in GA1, such as glutaconate, are toxic to the extrapyramidal tract system in the central nervous system, and that the clinical symptoms of the patients are attributable to atrophy of basal ganglia. Brain CT may be useful in diagnosis and evaluation of the clinical course of GA1 patients.

Muscle histochemistry in myotubular (centronuclear) myopathy.

We report the clinical and histochemical findings in 7 patients with myotubular (centronuclear) myopathy aged from 2 months to 32 years. The clinical symptoms varied from patient to patient. Three patients developed severe muscle weakness and hypotonia with respiratory distress from infancy, and 4 had muscle weakness from 2-5 years of age with no apparent delay in developmental milestones. In addition to an increased number of fibers with centrally placed nuclei, there were 3 other histochemical characteristics of this disorder, i.e., type 1 fiber predominance, type 1 fiber hypotrophy and type 2B fiber deficiency. Other histological findings included a peripheral halo in the sarcoplasm on NADH-TR staining and an increased number of undifferentiated type 2C fibers, indicating a delay in muscle fiber growth and differentiation due to a probable defective neural supply in the developing muscles.

Muscle pathology in cytochrome c oxidase deficiency.

Muscle biopsies from 16 patients with cytochrome c oxidase (CCO) deficiency were examined morphologically. Two siblings had the fatal infantile form. The muscle of the older sister at the age of 5 months had numerous ragged-red fibers (RRF) and increased numbers of lipid droplets; at 28 days the brother had no RRF suggesting that the RRF formed later than 28 days. The muscle pathology in two patients with the benign infantile form improved as they grew older; numbers of RRF, lipid droplets and glycogen particles decreased and CCO activity increased in the second biopsy. In the encephalomyopathic form, RRF were seen in 5 of 12 muscles mostly in patients more than 6 years of age. Muscle spindles and blood vessel walls in the biopsies from three patients with rapid clinical aggravation had no CCO activity, suggesting that enzyme activity differed from tissue to tissue (tissue specificity).