Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report an 84-year-old man with marked dropped head from 80 years of age. On neurologic examination, weakness was restricted to the neck extensor muscle, and the range of motility (ROM) of cervical spine was limited. He also had vascular parkinsonism. Needle electromyography indicated myogenic changes localized in the cervical paraspinal and trapezius muscles. CT and MRI of the cervical region demonstrated neck extensor muscle atrophy. Cervical paraspinal muscle biopsy revealed decreased numbers of muscle fibers which were embedded in markedly increased connective tissue. There was neither cellular infiltration nor specific changes. These findings were identical to those seen in isolated neck extensor myopathy recently proposed by Katz et al. (1996). In addition, pathological finding of the biceps muscle of the left arm suggested subclinical general myopathy because of mild fiber-size variability with moth-eaten appearance on NADH-TR straining. Neck extensor muscle weakness and limitation of ROM improved by physical therapy, and gait disturbance also improved simultaneously. To our knowledge, this is the first report isolated neck extensor myopathy in Japanese.
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PMID:[A case of isolated neck extensor myopathy with parkinsonism]. 929 26

We present a family with severe exercise intolerance, progressive proximal weakness, and lactic acidemia. Fifteen of 24 family members in five generations were affected. Since the affected males do not have offspring at this time, the family pedigree is consistent with either maternal or autosomal dominant inheritance. Muscle histochemistry showed ragged-red fibers and electron microscopy showed globular mitochondrial inclusions. Biochemical analysis showed reduced muscle activities of mitochondrial NADH-cytochrome c reductase (1 of 2 patients), succinate-cytochrome c reductase (2 patients), and cytochrome c oxidase (2 patients). For 1 patient, sequence analysis of 44% of the muscle mitochondrial DNA including all 22 transfer RNA regions showed no point mutation with pathogenic significance. Southern blot analysis showed no deletion. Six affected members of the family were treated with methylprednisolone (0.25 mg/kg) for 3 months. Muscle strength, serum lactate, and energy metabolism at rest (measured by 31P magnetic resonance spectroscopy) significantly improved with treatment.
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PMID:Biochemical and genetic studies in a family with mitochondrial myopathy. 932 76

We describe a neonate with hypotonia, weakness, early death owing to respiratory failure, and a severe form of arthrogryposis multiplex congenita. Postmortem studies revealed numerous ragged-red fibers and central nervous system abnormalities consistent with a mitochondrial disease. No NADH:ubiquinone-1 oxidoreductase (complex I) activity could be detected in skeletal muscle. These findings suggest that mitochondrial cytopathies can be associated with arthrogryposis multiplex congenita and should therefore be sought in neonates presenting with severe arthrogryposis.
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PMID:Ragged-red fibers and complex I deficiency in a neonate with arthrogryposis congenita. 939 Jul 2

Although disorders of thyroid function may cause a wide range of muscle disturbances, an overt myopathy has been rarely reported as an isolated clinical presentation of hypothyroidism. We observed 10 patients (5 males and 5 females) who had been referred to the department of neurology because of muscular fatigability, myalgia, cramps, or proximal weakness. Laboratory investigation showed that all patients had hypothyroidism due to Hashimoto's thyroiditis (atrophic variant in 9/10). Classic symptoms/signs of hypothyroidism such as lethargy, constipation, cold intolerance, myxedematous facies, and/or bradycardia were absent, as assessed independently by the three coauthoring thyroidologists. Muscular complaints improved greatly and then disappeared after substitutive levothyroxine treatment. Muscle biopsy revealed nonspecific changes. Nicotinamide adenine dinucleotide reductase (NADH-TR)-hyporeactive cores were present in two patients (10% and 90% of type 1 fibers). On electron microscopy, the core areas showed disorganized myofibrils, Z-band streaming, rod formation, and paucity of mitochondria and glycogen granules. Desmin intermediate filaments were overexpressed only in some cores. The similarity of the pattern of desmin expression between hypothyroid cores and target lesions of denervated fibers supports the hypothesis that, at least in some of our patients, myopathy was the result of an impaired nerve-mediated action of thyroid hormones on skeletal muscle. Our observations suggest that an isolated myopathy as the sole manifestation of hypothyroidism is not a rare event. We postulate that our cases may constitute a peculiar subgroup of Hashimoto's thyroiditis patients: (1) the strikingly abnormal F/M ratio of 1:1; (2) the relatively younger age; (3) the rarity of the goitrous variant; (4) the unusual finding of antithyroglobulin (Tg-Ab) > antithyroid peroxidase (TPO-Ab). Thorough evaluation of thyroid function is appropriate in patients with myopathy of uncertain origin.
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PMID:Myopathy as the persistently isolated symptomatology of primary autoimmune hypothyroidism. 984 19

Case 1: A 27-year-old man had a fever of 38 degrees C, followed by acute onset of bilateral upper arm pain. Two days later severe muscle weakness in bilateral upper arms appeared and he was admitted to our hospital. On admission, severe atrophy of the left deltoid and mild atrophy of the right deltoid were observed, with severe muscle weakness in bilateral deltoid and mild weakness in other parts of upper extremities. Tendon reflexes were decreased in the upper extremities. Sensation was intact. CSF showed mild pleocytosis. Nerve conduction velocity was normal and electromyography showed mild NMU decrease in upper extremities. Muscle biopsy of the right deltoid one month after the onset was normal. Muscle weakness began to improve 3 months after the onset, with only mild weakness at 10 months. Case 2: A 60-year-old man had acute onset of left shoulder and upper arm pain, followed by muscle atrophy and weakness of the left upper arm. He showed marked atrophy of the left deltoid, moderate atrophy of the left biceps and left scapular region, and severe muscle weakness in the left upper arm. Deep tendon reflexes were absent in the left upper extremity. Sensation was intact. Nerve conduction velocity was normal and electromyography showed marked NMU decrease in the left upper arm. Muscle biopsy of the left biceps 4 months after the onset showed grouped atrophies on HE staining, type 2 fiber atrophies on routine ATPase staining, and many targetoid atrophic fibers on NADH-TR staining. Muscle weakness began to improve slowly 6 months after the onset, but considerable weakness persisted at 10 months. Detailed muscle biopsy findings in neuralgic amyotrophy have not been documented. Muscle biopsy of Case 2 showed marked neurogenic changes compared to Case 1, which may be associated with the difference in clinical course between the two cases.
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PMID:[Two cases of neuralgic amyotrophy]. 986 14

We report the first molecular defect in an NADH-dehydrogenase gene presenting as isolated myopathy. The proband had lifelong exercise intolerance but no weakness. A muscle biopsy showed cytochrome c oxidase (COX)-positive ragged-red fibers (RRFs), and analysis of the mitochondrial enzymes revealed complex I deficiency. Sequence analysis of the mitochondrial genes encoding the seven NADH-dehydrogenase subunits showed a G-to-A transition at nucleotide 11832 in the subunit 4 (ND4) gene, which changed an encoded tryptophan to a stop codon. The mutation was heteroplasmic (54%) in muscle DNA. Defects in mitochondrially encoded complex I subunits should be added to the differential diagnosis of mitochondrial myopathies.
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PMID:Exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene. 1036 Jul 80

Hb-M is a very rare hemoglobinopathy in the Indian subcontinent. We report a family with Hb-M with lifelong cyanosis from the Ratnagiri district in western India. The propositus was a 11-year-old female child with a history of increasing cyanosis exacerbated by fever and weakness. Similar complaints were also noted in her mother and five maternal family members. There was no history of cardiac illness or exposure to drugs and chemicals. The methemoglobin level was 39.3% in the propositus and 21.1% in her mother with normal NADH-methemoglobin reductase activity. Abnormal absorption peaks by spectroscopic analysis, presence of hemoglobin instability, and a slow-moving band on starch gel electrophoresis supported the presence of Hb-M. Automated DNA sequence analysis of the beta globin gene showed a C-->T substitution at codon 63. This leads to a substitution of histidine (CAT) by tyrosine (TAT) at the beta 63 (E7) position, similar to Hb-M Saskatoon. We have named this variant as Hb-M(Ratnagiri).
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PMID:Congenital methemoglobinemia caused by Hb-MRatnagiri (beta-63CAT-->TAT, His-->Tyr) in an Indian family. 1592 17

Isometric force production and ATPase activity were determined simultaneously in single human skeletal muscle fibers (n = 97) from five healthy volunteers and nine patients with chronic heart failure (CHF) at 20 degrees C. The fibers were permeabilized by means of Triton X-100 (1% vol/vol). ATPase activity was determined by enzymatic coupling of ATP resynthesis to the oxidation of NADH. Calcium-activated actomyosin (AM) ATPase activity was obtained by subtracting the activity measured in relaxing (pCa = 9) solutions from that obtained in maximally activating (pCa = 4.4) solutions. Fiber type was determined on the basis of myosin heavy chain isoform composition by polyacrylamide SDS gel electrophoresis. AM ATPase activity per liter cell volume (+/-SE) in the control and patient group, respectively, amounted to 134 +/- 24 and 77 +/- 9 microM/s in type I fibers (n = 11 and 16), 248 +/- 17 and 188 +/- 13 microM/s in type IIA fibers (n = 14 and 32), 291 +/- 29 and 126 +/- 21 microM/s in type IIA/X fibers (n = 3 and 5), and 325 +/- 32 and 205 +/- 21 microM/s in type IIX fibers (n = 7 and 9). The maximal isometric force per cross-sectional area amounted to 64 +/- 7 and 43 +/- 5 kN/m(2) in type I fibers, 86 +/- 11 and 58 +/- 4 kN/m(2) in type IIA fibers, 85 +/- 6 and 42 +/- 9 kN/m(2) in type IIA/X fibers, and 90 +/- 5 and 59 +/- 5 kN/m(2) in type IIX fibers in the control and patient group, respectively. These results indicate that, in CHF patients, significant reductions occur in isometric force and AM ATPase activity but that tension cost for each fiber type remains the same. This suggests that, in skeletal muscle from CHF patients, a decline in density of contractile proteins takes place and/or a reduction in the rate of cross-bridge attachment of approximately 30%, which exacerbates skeletal muscle weakness due to muscle atrophy.
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PMID:Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure. 1605 11

We report a novel homozygous mutation responsible for NADH-b(5)R deficiency in a family from Ratnagiri district in western India with recessive congenital methemoglobinemia (RCM) type I. The propositus was a 20-year-old female with a history of increasing cyanosis exacerbated by fever and weakness. There was no history of cardiac illness or exposure to drugs and chemicals. The methemoglobin level was 38.0% in the propositus with 70% reduction in NADH-b(5)R activity. Spectroscopic analysis of the hemolysate showed normal peaks suggesting absence of Hb-M. There was no hemoglobin instability and G6PD activity was normal. This novel G-->A homozygous mutation at codon 143 in exon 5 was identified by SSCP followed by DNA sequencing and results in a glycine to aspartic acid substitution in the cytochrome b(5) reductase protein. This mutation, which is located outside the FAD and NADH binding domain, leads to mild cyanosis. Investigations of the family members revealed that both the parents and a brother of the propositus were heterozygous for the G143D mutation.
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PMID:A novel G143D mutation in the NADH-cytochrome b5 reductase gene in an Indian patient with type I recessive hereditary methemoglobinemia. 1796 95

The Silent Corticotroph Adenoma (SCA) is a pituitary adenoma variant characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH) and related peptides, without the clinical signs of Cushing's disease. SCA has been postulated to either secrete structurally abnormal ACTH that is inactive but detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH intermittently or at low levels continuously. Excess of ACTH has been associated to type II muscle atrophy. We describe a case of type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. The dog showed moderate to severe proximal muscle wasting and weakness with normal levels of muscle-associated enzymes. In the limb muscle biopsies, type II fibers were uniformly smaller than type I fibers. In temporalis muscles, there were few atrophic fibers, and several irregular areas of loss of enzymatic activity observed in NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and immunohistochemical analysis demonstrated the presence of cytoplasmic immunoreactivity for ACTH. The muscle atrophy was considered to be related to an excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals could help to understand the mechanism of similar diseases in human has well.
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PMID:Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. 2107 46


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