Search

Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase (GNE).

To characterize the clinical diagnostic features, neuropathologic phenotype of tau deposition, and subunit structure of tau filaments in patients who had an asparagine-to-lysine substitution at codon 279 (the N279K missense mutation) of the gene for microtubule-associated tau protein.

The authors studied the pathomechanisms of the characteristics associated with Gerstmann-Sträussler-Scheinker disease (GSS).

A case of neoplastic angioendotheliosis demonstrating unusual manifestations is reported. A 56-year-old male showed recurrent attacks of neurological symptoms including paraplegia, brain-stem symptoms, tonic seizures, aphasia, apraxia and cortical blindness over 2 years. The EEG disclosed transient, periodic, lateralized, epileptiform discharges. Brain CT scan revealed low-density areas mainly in the white matter. Other laboratory examinations were negative except for CSF protein fractions. Post-mortem examination disclosed remarkable intravascular proliferation of atypical cells in the CNS with prominent proliferation of blood vessels and softening. Other organs were not affected, which suggested that the atypical cells had a high affinity to CNS blood vessels.

Four patients with mitochondrial abnormality had multiple muscle biopsies at several year intervals during which respiratory chain enzyme activities were shown to be quite variable. In three patients, progression of the disease paralleled the decrease in respiratory chain enzyme activity. In one patient, the clinical and pathological findings improved with age as is seen in the benign infantile form of cytochromec oxidase (CCO) deficiency. The variability in these mitochondrial disorders may result from the varied proportions of normal and abnormal mitochondria in the muscle cells in which the mitochondria are said to be randomly replicated from numerous mitochondrial DNA copies.

X-linked dystrophinopathy is the most common cause of isolated cases of myopathy in males. To investigate dystrophin abnormalities as a cause of myopathy in girls and women, we used dystrophin immunocytochemistry to study muscle biopsies from 505 girls and women with neuromuscular disease. Forty-six muscle biopsies showed a combination of fibers containing or lacking dystrophin; this mosaic immunostaining pattern denoted a carrier status. Twenty-one of 46 (45.6) had a family history of Duchenne muscular dystrophy in males. Twenty-five of 46 (54.3) were isolated cases, with no previous family history of neuromuscular disorder. The laboratory findings of the isolated cases were consistent with the familial cases; all showed myopathic histopathology and abnormal elevations of serum CK. The clinical presentations of the isolated cases varied but were consistent with the familial cases: 40 (10/25) of isolated cases showed proximal limb weakness before age 10, 24 (6/25) presented with myalgias or cramps, 24 (6/25) presented with incidental findings of grossly elevated CK levels, 8 (2/25) noted easy fatigue, and 4 (1/25) had slowly progressive proximal limb weakness beginning at age 45. From our data, the clinical criteria for consideration of an underlying dystrophinopathy in isolated female cases of myopathy are CK levels greater than 1,000 IU/1 and myopathic histopathology. About 10 of the isolated cases of hyperCKemic myopathy (25/210) were proven by dystrophin analysis to have a dystrophinopathy as the cause of their disease (manifesting carriers of Duchenne dystrophy). However, we feel that this may be an underestimate. The correct diagnosis in these patients is imperative for appropriate genetic counseling to the patients and their families.

A case of a unique combination of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like syndrome (MELAS) with acanthocytosis is reported. Neuropathological examination revealed pellagra-like change in Betz cells, brain-stem neurons and anterior horn cells as well as findings compatible with mitochondrial encephalomyopathies. Abnormal function of nicotinic acid-related enzymes could be the cause of the complicated clinicopathologic findings in this case. This is the first report of MELAS with acanthocytosis.

Immunoblot characterization and immunofluorescence localization of dystrophin are presented for 76 human patients with various neuromuscular diseases. Normal dystrophin (shown by immunoblotting) was invariably visualized as a continuous, peripheral membrane immunostaining of myofibers. Biochemical abnormalities of dystrophin (either lower or higher molecular weight dystrophin) resulted in patchy, discontinuous immunostaining, suggesting that the abnormal dystrophin proteins are not capable of creating a complete membrane cytoskeleton network. There was a very strong correlation of clinical diagnoses with the type of dystrophin abnormality; all Duchenne muscular dystrophy patient muscle contained no detectable dystrophin, Becker muscular dystrophy patient muscle had clearly abnormal dystrophin, and unrelated diseases showed normal dystrophin. However, a single patient of five carrying the diagnosis of Fukuyama dystrophy showed no detectable dystrophin and thus appeared to be a Duchenne dystrophy patient by the biochemical assays. We know of no other case of a patient with a disease thought to be unrelated to Duchenne/Becker dystrophy yet demonstrating dystrophin deficiency. Based on the data presented, we conclude that immunofluorescence is the best technique for the detection of female carriers of Duchenne dystrophy, whereas immunoblotting appears superior for the prognostic diagnosis of Becker muscular dystrophy.

The tauN279K mutation was identified in four separately ascertained families in the United States, Japan, and France and in another recently discovered affected individual in Japan. The authors analyzed genealogical and clinical records and DNA samples. Average age at onset was 43 years; survival time was 7 years. All families exhibited similar clinical features, with parkinsonism, dementia, and supranuclear palsy uniformly seen. A founder effect indicated by a shared disease haplotype was seen only in two Japanese families. The N279K mutation can develop independently in different parts of the world.