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Biomedical subjects

S DiMauro

Publications and source records attributed to S DiMauro.

At least 343 records · Page 19Linked to original sources
PubMed1982

Encephalopathy and fatal myopathy in two siblings. Their association with partial deficiency of muscle carnitine.

Two brothers had intermittent episodes of muscle weakness, lethargy, hyperammonemia, rhabdomyolysis, and elevated activities of creatine phosphokinase (CPK), lactic dehydrogenase, and SGOT in serum associated with low muscle carnitine but normal serum carnitine concentrations. These siblings represent a "mixed" form of carnitine deficiency with the elements of both systemic and myopathic carnitine deficiency. The older sibling died suddenly after a 24-hour fast. The younger boy has received carnitine for three years. During this period, serum CPK activity has remained elevated and increased further during illnesses, but no clinical symptoms of encephalopathy or myopathy have appeared.

Carnitine↗
PubMed1982

Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.

We studied a boy who presented at age 3 1/2 years with cardiomegaly, a distinctive electrocardiogram, and a history of a brother dying with cardiomyopathy. From age 3 1/2 to 5 years, cardiac disease progressed, resulting in intractable congestive heart failure. Skeletal muscle weakness developed and a muscle biopsy showed lipid myopathy. Muscle and plasma carnitine were reduced to 2 and 10% of the normal mean values, respectively. Therapy with L-carnitine (174 mg/kg/da) was begun at age 5 1/2 years and continued to the present (age 6 1/2 years). The cardiac disease has resolved and the muscle strength has returned to normal. Plasma carnitine concentrations have risen to the low-normal range, while urinary carnitine excretion has increased to values which are 30 times normal. The renal clearance of carnitine exceeds normal at all plasma concentrations and plasma carnitine values do not change acutely after an oral carnitine load. These results suggest that there is a distinct form of carnitine deficiency which presents as cardiomyopathy and may be successfully treated with L-carnitine. A defect in renal and possibly gastrointestinal transport of carnitine is a likely cause of this patient's disorder.

Cardiomyopathies↗
PubMed1982

Muscle phosphoglycerate mutase deficiency.

A 52-year-old man complained since adolescence of cramps and pigmenturia after 15 to 30 minutes of intense exercise. There was no family history of neuromuscular diseases, and strength was normal. The rise of venous lactate after forearm ischemic exercise was abnormally low. Histochemical and ultrastructural studies of a muscle biopsy showed mild increase of glycogen, which was confirmed by biochemical analysis. Studies of anaerobic glycolysis in vitro showed decrease lactate formation with glycogen and with all hexosephosphate glycolytic intermediates, suggesting a defect below the phosphofructokinase reaction. Muscle phosphoglycerate mutase (PGAM) activity was 5.7% of the lowest control, while all other enzymes of glycolysis had normal activities. Electrophoretic, heat lability, and mercury inhibition studies showed that the small residual activity of PGAM in the patient's muscle was represented by the brain (BB) isoenzyme, suggesting a genetic defect of the M subunit that predominates in normal muscle. The prevalence of the BB isoenzyme in other tissues, including muscle culture, may explain why symptoms were confined to muscle.

Adult↗
PubMed1982

Familial myoadenylate deaminase deficiency and exertional myalgia.

In 14 members of four families with a hereditary syndrome of exertional myalgia, five of eight muscle biopsies from symptomatic individuals showed histochemical and biochemical absence of myoadenylate deaminase (MADA). In the others, MADA biochemical activity was normal in two and reduced but not absent (intermediate level) in one. Asymptomatic relatives had normal histochemical MADA activity, but three had intermediate biochemical levels. In a survey of 302 routine muscle biopsies, 3 of 36 patient with myalgia had absence of MADA. Three of 266 biopsied for other conditions were MADA-deficient. Despite some inconsistencies, MADA deficiency seems to be relevant to this clinical syndrome.

AMP Deaminase↗
PubMed1981

Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy.

Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest control value) in a 52-year-old man with intolerance for strenuous exercise and recurrent pigmenturia since adolescence. All of the other enzymes of glycolysis had normal activities, and glycogen concentration was normal. Electrophoretic, heat lability, and mercury inhibition studies showed that the small residual activity in the patient's muscle was represented by the brain (BB) isoenzyme of phosphoglycerate mutase, suggesting a genetic defect of the M subunit which predominates in normal muscle. The prevalence of the BB isoenzyme in other tissues, including muscle culture, may explain why symptoms were confined to muscle.

Brain↗
PubMed1981

Glycogen debrancher deficiency is reproduced in muscle culture.

Muscle cultured from two adults with debrancher deficiency myopathy showed abnormal glycogen deposits by electron microscopy. Glycogen debranching activity was markedly decreased, but phosphorylase activity was normal. Lack of glycogen debranching activity in muscle cultures from debrancher-deficient patients contrasts with the presence of a fetal isoenzyme of phosphorylase in muscle cultured from patients with McArdle disease and suggests that the genetic control of the debranching enzyme does not change during muscle development.

Adult↗
PubMed1981

Mucolipidosis II (I-cell disease): studies of muscle biopsy and muscle cultures.

Muscle cultures from a patient with I-cell disease showed the characteristic morphologic and biochemical abnormalities previously observed in cultured fibroblasts. At early stages of myoblast growth, there were numerous inclusions. Biochemically, the intracellular activities of beta-galactosidase, beta-hexosaminidase, and alpha-mannosidase were reduced to 1, 14, and 5%, respectively, of control values, and this was accompanied by elevated levels of beta-hexosaminidase and alpha-mannosidase in the culture medium. Cultures from the patient did not fuse as well as controls; however, when well-developed myotubes possessing distinct cross-striations were present, these no longer had inclusions. In the muscle biopsy from this patient, only beta-galactosidase was decreased to approximately 50% of the mean control value whereas beta-hexosaminidase and alpha-mannosidase activities were increased as compared to controls. These data suggest that the I-cell mutation is expressed during early myogenesis but not in well-differentiated myotubes or mature muscle fibers.

Biopsy↗
PubMed1981

Lysosomal glycogen storage disease with normal acid maltase.

Two unrelated 16-year-old boys had mental retardation, cardiomegaly, and proximal myopathy. One also had hepatomegaly. Histochemistry and electronmicroscopy of muscle biopsies showed lysosomal glycogen storage resembling acid maltase deficiency. Biochemical studies of skeletal muscle showed increased content of glycogen of normal structure; acid alpha-glucosidase activity in both urine and muscle was normal. Other enzymes of glycogen metabolism were also normal. The cause of this apparently generalized glycogenosis with no demonstrable enzyme defect is unknown.

Acid Phosphatase↗
PubMed1981

Muscle phosphofructokinase deficiency: abnormal polysaccharide in a case of late-onset myopathy.

A 61-year-old woman with muscle phosphofructokinase (PFK) deficiency had mild limb weakness all her life but no cramps or myoglobinuria. For 5 years the limb weakness progressed. In muscle, PFK activity was 1% of normal and glycogen concentration was elevated (2.13%). By light microscopy, a minor component of the accumulated glycogen appeared as PAS-positive, diastase-resistant inclusions in 10% of muscle fibers. The inclusions had a filamentous fine structure that resembled the abnormal long-chain glycogen of brancher enzyme deficiency. Iodine absorption spectra of both the inclusions and a diastase-resistant fraction of isolated glycogen resembled amylopectin. The abnormal polysaccharide in PFK deficiency may be related to greatly elevated concentration of muscle glucose-6-phosphate, an activator of the chain-elongating enzyme glycogen synthase.

Child↗
PubMed1980

Myoadenylate deaminase deficiency--muscle biopsy and muscle culture in a patient with gout.

AMP deaminase activity was undetectable by a sensitive spectrophotometric assay in the muscle biopsy of a 37-year-old man with gout and exercise-related cramps and myalgia. Venous ammonia failed to rise after ischemic exercise, but the diagnostic value of this test is uncertain because changes of plasma ammonia after exercise varied greatly in different normal individuals. In the patient, AMP deaminase activity was normal not only in erythrocytes, leukocytes and cultured fibroblasts but also in muscle cultures. Presence of AMP deaminase in muscle cultures was probably due to the expression of a fetal isoenzyme under separate genetic control from adult muscle AMP deaminase.

AMP Deaminase↗
PubMed1980

Carnitine palmityl transferase deficiency: myoglobinuria and respiratory failure.

A 51-year-old man presented with acute respiratory failure and myoglobinuria precipitated by an infection. Carnitine palmityltransferase (CPT) deficiency was documented in muscle, leukocytes, and liver. The enzyme defect in liver, previously suspected and now documented, explained the decreased production of ketone bodies during fasting observed in this patient as well as others with muscle CPT deficiency. Decreased utilization of long-chain fatty acids and decreased availability of ketone bodies can deprive the muscle of crucial sources of energy and, in certain conditions, may precipitate myoglobinuria.

Acyltransferases↗
PubMed1980

Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency.

A 1-month-old boy was admitted because of failure to thrive. He was floppy and had bilateral ptosis, diminished reflexes, and poor suck. He had aspiration pneumonia, developed seizures, and died at age 3 1/2 months. Laboratory data showed lactic acidosis, proteinuria, glycosuria and generalized aminoaciduria. He was an only child, and family history was negative. Muscle biopsy showed large clumps of granules positive with oxidative enzyme stains and increased lipid droplets. Ultrastructural studies showed large aggregates of mitochondria, many of which were greatly enlarged and contained disoriented or concentric whorls of cristae and paracrystalline inclusions. Cytochrome c oxidase was absent in fresh frozen sections by histochemical staining. By biochemical assay, cytochrome c oxidase (cytochrome aa3) was 6% of normal in muscle biopsy and undetectable in autopsy muscle; spectra and content of cytochromes showed lack of cytochrome aa3, decreased cytochrome b and normal cytochrome cc1. In kidney, cytochrome-c-oxidase activity was 38% of normal and spectra showed decreased cytochromes aa3 and b. The association of fatal infantile mitochondrial myopathy, lactic acidosis and renal dysfunction was previously reported by Van Biervliet et al and appears to be a distinct nosologic entity, one of the few biochemically defined mitochondrial myopathies.

Carnitine O-Palmitoyltransferase↗
PubMed1979

Adult polysaccharidosis. Clinicopathological, ultrastructural, and biochemical features.

An abnormal polysaccharide in the form of cytoplasmic spheroids was found in the nervous system and systemic organs of a man with a progressive neurological disorder characterized by onset at 47 years of age, severe weakness, sensory loss, and dementia. Results of biochemical analysis showed a marked increase in brain and heart polysaccharide that was resistant to digestion by a mixture of glucosidases and that exhibited an iodine-complex spectrum higher than that of normal glyocgen. Results of histochemical studies were consistent with the results of biochemical analysis and further defined the branching characteristics of the stored polysaccharide. Electron microscopy showed the cytoplasmic location of the spheroids, which were granular and filamentous.

Amylopectin↗