Myophosphorylase deficiency: two different molecular etiologies.

Two different forms of myophosphorylase deficiency (McArdle's disease) can be distinguished through the presence or absence of the protein subunit corresponding to phosphorylase in muscle extracts analyzed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Two patients showed a complete absence of the phosphorylase protein subunit, while another patient had an increased quantity of an apparently defective phosphorylase protein subunit. On the basis of these observations, the existence of two distinct subtypes of phosphorylase deficiency can be inferred.     

Dystrophin deficiency in a case of congenital myopathy

Summary We studied a 5-year-old boy who had the floppy infant syndrome and a dystrophic pattern on muscle biopsy. According to the clinical presentation and the histopathological findings the diagnosis of congenital muscular dystrophy with associated intellectual retardation was made. Immunohistochemical and immunoblot studies using anti-dystrophin antibodies showed complete absence of the protein in the patient's muscle. DNA analysis using cDNA probes showed a deletion at the 5 end of the dystrophin gene. Our observations on this patient suggest a new phenotypical variant of Duchenne muscular dystrophy.     

Polyglucosan body disease myopathy: an unusual presentation

Polyglucosan body disease (PBD) is a slowly progressive adult-onset glycogen storage disorder that typically affects upper and lower neurons. Myopathy, as a complication of PBD has been reported rarely and clinically manifests as chronic limb-girdle muscle weakness. We report an unusual case of PBD myopathy presenting as an asymmetric motor syndrome that clinically overlapped with amyotrophic lateral sclerosis, further expanding the phenotype of this disorder.     

Oculopharyngeal myopathy with inflammation and calcinosis: an unusual phenotype

The case is reported of a patient with progressive proximal and distal weakness, dysphagia, respiratory weakness, calcifications, ptosis and ophthalmoparesis with inflammation, rimmed vacuoles and positive amyloid and ubiquitin on muscle biopsy. The histopathological features fit best with inclusion body myositis, but ophthalmoparesis and ptosis have not previously been described. The clinical phenotype fits best with hereditary inclusion body myopathy or distal-oculopharyngeal muscular dystrophy, but the degree of inflammation seen is unusual. None of these are associated with calcinosis.     

Myophosphorylase deficiency (McArdle's disease): report of a family.

The clinical and biochemical findings are presented of two brothers suffering from McArdle's Disease (Myophosphorylase Deficiency). Tissue enzyme estimations and lactate levels were done in affected and non-affected members of the family. Affected members showed absence of phosphorylase enzyme by histochemical and quantitative estimation. No quantitative abnormalities were found in other enzyme systems of glycolytic pathways in the family investigated. Various other aspects of clinical features, biochemical abnormalities and inheritance are discussed.     

Case report Myophosphorylase deficiency and limb-girdle muscular dystrophy in the same pedigree

We report 2 familial patients with limb-girdle muscular dystrophy (LGD). The parents of patient 1 showed a consanguineous marriage and patient 2 was a paternal cousin of patient 1. Slowly progressive muscular weakness/wasting and dystrophic changes in the biopsied muscles were observed in both patients. However, a quantitative assay revealed a severely reduced myophosphorylase activity in patient 1 with normal activity in patient 2. A semi-ischemic exercise test disclosed no elevation of venous lactate in patient 1 with a normal increase in patient 2. A leukocytes DNA analysis in patient 1 did not show the gene deficits previously recognized in patients with McArdle's disease (McD). Patient 1 may only have abnormal myophosphorylase activity with dystrophic changes secondary to the myophosphorylase deficiency or coincidentally two genomic abnormalities for McD and LGD. LGD still has heterogenous etiologies and the responsible genes for these two disorders may be closely mapped.     

Primary carnitine deficiency: adult onset lipid storage myopathy with a mild clinical course

We studied two adult patients with myalgia and muscular fatigability during prolonged physical exercise. Serum creatine kinase was increased and muscle biopsy revealed a lipid storage myopathy affecting predominantly the type I fibres. Skeletal muscle carnitine content was reduced to 15% and 21% of the normal mean values, while serum carnitine levels were either normal or decreased. Four months of oral therapy with L-carnitine (3 g per day) resolved the clinical symptoms completely in both patients, and a subsequent muscle biopsy confirmed a marked reduction of lipid storage, along with increased muscle carnitine levels. The analysis of renal carnitine excretion and the exclusion of possible secondary carnitine deficiencies in both patients are compatible with mild defects of the carnitine transporter in one patient and of carnitine biosynthesis in the other. Since myalgia and muscular fatigue are frequent but unspecified complaints of otherwise clinically unremarkable adult patients, it is important to identify myopathies associated with primary carnitine deficiency because they may be amenable to treatment.     

Follow-up studies in a case of unusual congenital myopathy,suggestive of nemaline type

Summary A 20-month-old boy — offspring of consanguinous parents, whose mother presumably had subclinical myopathy — presented with clinical signs of congenital non-progressive myopathy, neurogenic-myogenic electromyographic findings and normal motor conduction velocity. Biopsy of quadriceps muscle showed fiber-type disproportion with hypotrophic type 1, hypertrophic 2A and absent 2B fibers. Subsarcolemmal segmental foci of abnormally, in part regularly arranged bundles of mostly thin myofilaments were found in 13% of hypotrophic type 1 fibers. Rods were seen in only 1 fiber out of 20 tissue blocks. Reexamination 6 years later revealed slightly increased muscle force, myopathic EMG pattern and borderline motor and sensory nerve conduction velocities. Biopsy specimen from deltoid muscle consisted of untypable fibers of varying diameters with jagged Z-lines and increased variability of myofibrillar diameters. Multiple rods were present in 1% of the fibers, the formerly seen segmental foci in 0.1% only. Several intramuscular nerves were normal. The case contributes some new features to the spectrum of congenital myopathies of the nemaline type and suggests different stages of arrested maturation of type 1 fibers at least in this particular case.     

Biochemical and immunologic studies in a case of congenital myopathy with unusual morphologic features

Mitochondria and myosin were isolated from a muscle biopsy of a 9-year-old boy with an unusual congenital myopathy characterized by type I fiber uniformity, jagged Z-line, and transverse network hypertrophy of mitochondria. Biochemical examination of isolated mitochondria showed that only citrate synthase activity was significantly reduced. Electrophoresis of myosin heavy chains and immunoenzymatic analysis of myosin heavy and light chains with antibodies specific to either fast or slow myosins showed that only the slow-type isoform of myosin was detectable. Indirect immunofluorescence of muscle biopsy showed that all muscle fibers homogeneously expressed only the slow type of myosin.     

Cytopathology of an unusual case of centronuclear myopathy: Light- and electron-microscopic investigations

The results of enzyme-histochemical and electron-microscopic investigations of a patient with centronuclear myopathy combined with targets, cores and prevalence of type-I fibers are presented. The patient had suffered from perinatal hypoxic brain damage, causing enlargement of the ventricular system, slight frontal atrophy and right-sided hemiparesis. Morphologic investigation of muscle fibers demonstrated dynamic activity of an autophagic system represented by a distinct increase of Golgi components adhering to the nuclear surface. By analysing the lytic events and their sequences, a postnatal secondary migration of subsarcolemmal nuclei to the central regions of muscle fibers can be postulated.     

Zebra body myopathy: a second case of ultrastructurally distinct congenital myopathy

Biopsy of the deltoid muscle of a 4-day-old baby boy with congenital hypotonia and weakness showed zebra bodies and other myopathic changes. Our patient and an other patient reported in the literature establish zebra body myopathy as an ultrastructurally distinct benign congenital myopathy.     

Genetics of congenital nemaline myopathy

Family patterns for 50 reported probands with congenital nemaline myopathy were compared with expected patterns derived from various possible genetic hypotheses. The disease had a high mortality in childhood but remained clinically stationary after this period. Some normal relatives showed nemaline rods on muscle biopsy. Chromosomes were normal in the two cases in which they were examined. Prenatal exposures appeared irrelevant to this disease. Autosomal recessive and X-linked recessive or dominant modes of inheritance were not compatible with the observed patterns, which could be explained by an autosomal dominant mode with a reduced penetrance. Normal relatives who carried rods were presumably unaffected heterozygotes of the same gene. The genetic ratio (the proportion of affected siblings) was 0.3, being short of the expected value, 0.5, probably because of the presence of these asymptomatic rod-bearing heterozygotes. While the pressure of natural selection was great in the patients who died or were severely disabled, the gene could be passed to the next generation by mildly affected patients or heterozygotes who remained unaffected.     

Nonspecific congenital myopathy (minimal change myopathy): a case report

A 28-month-old male with generalized hypotonia and muscle weakness, a myopathic face, skeletal dysmorphism and delayed motor milestones from birth is reported. He gradually developed the ability of sitting and rolling over, but could not stand without support until 28 months. There was no intellectual impairment or seizures. Deep tendon reflexes were absent. The serum CK value, peripheral nerve conduction velocity and EMG were within normal limits. A muscle biopsy specimen showed mild variation in fiber size, and an increased number of type 2C fibers on histochemical examination, but no apparent abnormalities on electron microscopy. The baby was tentatively diagnosed as having minimal change myopathy or nonspecific congenital myopathy which is thought to be one of the congenital nonprogressive myopathies.     

Recurrent seizures: an unusual manifestation of vitamin B12 deficiency

The present report highlights an unusual presentation of vitamin B12 deficiency--recurrent seizures in a 26-year-old man. His symptoms responded to parenteral vitamin B12 therapy. The relevant literature is reviewed.     

Unusual course of nemaline myopathy

A boy with onset features common for a moderate form of congenital nemaline myopathy, after some years developed scapulo-humeral syndrome. Extra- and intrafusal muscle fibers overloaded with rods and indicating focal degenerative changes were seen in the first biopsy. The biopsy was later repeated and revealed an improvement in muscle architecture with a dramatically decreased number of rods. This transformation suggests that rods, as well as Z-line streaming, might be a reversible anomaly of Z-discs.