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alpha-Mannosidosis is an autosomal recessive lysosomal-storage disorder caused by a deficiency of lysosomal alpha-mannosidase activity. This disease shows a wide range of clinical phenotypes, from a severe, infantile form (type I), which is fatal at

A new homozygous alpha-sarcoglycan (adhalin) gene mutation was found in a Japanese patient with severe childhood autosomal recessive muscular dystrophy (SCARMD). Muscle biopsy specimens from the patient showed marked reduction but not complete deficiency of alpha-sarcoglycan. The sequence of part of exon 3 of the alpha-sarcoglycan gene exhibited a cytosine to thymidine substitution at nucleotide position 220. Since the same mutation was not found in 100 normal control samples, this new alpha-sarcoglycan gene mutation is not a polymorphism but is presumed to be responsible for the marked reduction of alpha-sarcoglycan in skeletal muscle. Most patients with homozygous alpha-sarcoglycan gene mutation were reported to show complete alpha-sarcoglycan deficiency. Present case showed the homozygous missense mutation of alpha-sarcoglycan and associated with incomplete alpha-sarcoglycan deficiency and severe clinical phenotype.

Cardiac function was examined in 21 patients with Becker muscular dystrophy (BMD) and compared with 43 patients with Duchenne muscular dystrophy (DMD) and 37 healthy control subjects. Electrocardiography showed myocardial damage was most frequently found in the lateral wall, compatible with autopsy findings. The ratio of the preejection period to the ejection time was higher in patients with BMD (0.37 +/- 0.07, mean +/- SD) than in patients with DMD (0.28 +/- 0.05) and healthy controls (0.23 +/- 0.04). Left ventricular dimension and mitral annular size at end diastole in patients with BMD increased to 52.3 +/- 7.7 mm and 28.8 +/- 5.3 mm with age, respectively. In patients with cardiac failure and BMD, mitral regurgitation was observed at a rate of 66.7%. No definite relation between the deleted locus of the dystrophin gene and cardiac failure was found. Because motor dysfunction progresses more slowly in BMD than in DMD, a prolonged work load on the morbid myocardium may lead to dilated cardiomyopathy with mitral regurgitation.

We purified the nicotinic acetylcholine receptor from digitonin-solubilized rabbit skeletal muscle by affinity chromatography and detected many proteins linked to AChR, including dystrophin, adhalin, beta-dystroglycan, utrophin, rapsyn, and actin. To determine whether or not AChR links to dystrophin-associated proteins (DAPs) without dystrophin, we studied the effects of denervation on AChR and DAPs in the skeletal muscle of a mdx mouse. Following surgical denervation, the levels of adhalin and beta-dystroglycan dramatically increased at the extrajunctional sarcolemma with AChR, suggesting that their association is independent of dystrophin. Furthermore, the diffuse extrajunctional appearance of adhalin, beta-dystroglycan, and AChR was observed after pharmacological denervation through the subcutaneous administration of succinylcholine. Since the depletion of DAPs and the subsequent disruption of sarcolemmal linkage are believed to be a primary cause of muscle cell necrosis in dystrophinopathies, pharmacological denervation may have some beneficial effect on these diseases.

Magnetic resonance imaging scans of the brain were obtained in 13 patients with myotonic dystrophy, seven with congenital myotonic dystrophy and six with adult-type myotonic dystrophy. All seven patients with congenital myotonic dystrophy had ventriculomegaly and a low IQ (DQ). Cerebral white matter lesions were observed in six cases, a small corpus callosum in four cases, a small brainstem in two cases, and a cerebellar white matter lesion in one case. Cerebral white matter lesions were observed in five of the six cases with adult-type myotonic dystrophy of which one had ventriculomegaly. The IQ (DQ) was significantly lower in patients with congenital myotonic dystrophy than in those with adult-type myotonic dystrophy. The incidence of a small corpus callosum or ventricular enlargement was higher in congenital myotonic dystrophy than in adult-type myotonic dystrophy. These findings may be related to the presence of neurologic impairment in congenital myotonic dystrophy.

The brain of patients with adult type myotonic dystrophy was measured using MRI, and compared with age- and sex-matched controls. The width of the cerebrum, and the areas of the corpus callosum, pons and pituitary gland were significantly smaller in adult-type myotonic dystrophy than in the controls. The IQ of the patients with adult-type myotonic dystrophy was lower than that of controls. These results demonstrate a decreased volume of the brain and pituitary glands in myotonic dystrophy. These findings suggest a causal relationship for the mental retardation and endocrine dysfunction that may occur.

Two siblings who exhibited hereditary parkinsonism with pyramidal signs and cerebellar ataxia are reported. Anticholinergics had a dramatic beneficial effect in both cases, but levodopa did not. This responsiveness, which is similar to that reported in patients with Joseph's disease, suggests dysfunction of an “indirect pathway” involving the globus pallidus and the subthalamic nucleus, in addition to that of the nigrostriatal system. We propose a new hereditary variant of early onset Parkinson's disease, distinct from the levodopa sensitive forms of juvenile Parkinson's disease.

There are no detailed reports about the clinical and pathological findings in the central nervous system (CNS) of patients with Becker’s muscular dystrophy (BMD), although dysfunctions of the skeletal and cardiac muscles are well known in BMD. Since dystrophin is present in the CNS, and usual medical treatment is often influenced by CNS manifestations in patients, we studied the clinical and pathological features of BMD, with particular focus on the CNS manifestations, and also examined the relationships of these features with skeletal and cardiac muscle dysfunctions. We examined eight BMD patients aged 24-77 years who were admitted to our hospital, and six autopsied BMD patients aged 39-58 years. In addition to family histories of the patients, clinical findings, and disease progression, BMD was diagnosed based on the presence of dystrophin revealed by immunohistochemical examination and examination of the dystrophin gene. Brain computed tomography (CT), magnetic resonance imaging (MRI), and CNS pathohistology were also performed. Gene analyses by multiplex PCR revealed that exons 3-4, 3-6, 12-19, 45-47,45-49, and 45-52 were deleted; all the deletions occurred in hot spots in the dystrophin gene. With regard to the clinical CNS manifestations of BMD, 2 of the 14 patients experienced hallucinations, but there was no patient with severe mental retardation. Brain CT and MRI scans revealed various grades of mild atrophy of the front-parietal lobe for all the patients. Low-magnification microscopy images of the brain of three autopsied patients with mild BMD showed that the gyri of the brain were separated, suggesting brain atrophy. The nerve cells of the frontal lobe, however, seemed to be unaffected histologically. These results show that there are mild abnormalities in the CNS of BMD patients. It is well known that BMD patients demonstrate different levels of skeletal and cardiac muscle dysfunctions. In the current study as well, the BMD patients demonstrated CNS abnormalities, although these abnormalities were mild compared to the skeletal and cardiac muscle dysfunctions.

A counterimmunoelectrophoresis technique for detection of serum myoglobin (Mb) was improved using non-ionic polymer dextran. Precipitin lines were graded according to their strength, which was ascertained by radioimmunoassay data. By this method, serum Mb in concentrations of 500 ng./ml. before stain and of 200 ng./ml. after stain were detected. Electrophoretic time was 60 minutes. Among 32 cases of acute myocardial infarction (AMI) whose blood samples were collected within 24 hours after disease onset, precipitin lines were detected in 25 cases (78 per cent) before stain and 31 cases (97 per cent) after stain. Considering the early peak concentration time (approximately 10 hours) of serum Mb after AMI onset, diagnosis becomes more rapid and exact with this method, especially in severe cases.