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)

Emery-Dreifuss dystrophy, an X-linked disorder, is a recently recognized distinct neuromuscular disease with special pediatric implications. We describe three affected boys with the typical early contractures and weakness. Two patients are from a large kindred that includes older affected males and carrier females, both of whom had lethal cardiac disease by mid-adulthood. The atrial arrhythmias are treatable by pacemaker if the diagnosis is established beforehand.
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PMID:Emery-Dreifuss muscular dystrophy. 670 17

Twelve girls and 2 boys with severe but not congenital muscular dystrophy were found in a national survey. An autosomal recessive gene is likely to account for most if not all of these cases. The condition differs slightly from X-linked Duchenne muscular dystrophy in showing prominent early toe-walking, a milder course, relatively more weakness of the deltoid muscles, normal intelligence, a normal ECG and a more focal pattern of muscle pathology.
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PMID:Severe muscular dystrophy in girls. 673 6

Histopathologic and ultrastructural findings in a muscle biopsy performed on an 11-year old boy with congenital hypotonia, weakness, respiratory insufficiency requiring chronic ventilatory support, and a probable X-linked inheritance are presented. The muscle biopsy disclosed a peculiar, ringlike arrangement of mitochondria and myonuclei in most muscle fibers. Accumulations of nemaline rods were present in approximately 10-15% of fibers. We believe that our patient represents a variant of myotubular/centronuclear myopathy. The histochemical findings suggest disturbance in developmental migration of nuclei and mitochondria probably due to impaired function of the cytoskeleton.
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PMID:Congenital myopathy with ringlike distribution of myonuclei and mitochondria and accumulation of nemaline rods. A variant of centronuclear myopathy? 754 14

We have previously shown in a large X-linked pedigree that a deletion removing the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin expression was present in the muscle of affected males and transcription studies indicated that this dystrophin originated from the brain and Purkinje cell isoforms, upregulated in this skeletal muscle. We have now studied dystrophin transcription and expression in the heart of one member of this family. In contrast to the skeletal muscle, dystrophin transcription and expression were absent in the heart, with the exception of the distal Dp71 dystrophin isoform, normally present in the heart. The 43- and 50-kD dystrophin-associated proteins were severely reduced in the heart, despite the presence of Dp71, but not in skeletal muscle. The absence of dystrophin and the down-regulation of the dystrophin-associated proteins in the heart accounted for the severe cardiomyopathy in this family. The mutation present in these males selectively affects dystrophin expression in the heart; this could be secondary to the removal of cardiac-specific regulatory sequences. This family may represent the first example of a mutation specifically affecting the cardiac expression of a gene, present physiologically in both the skeletal and cardiac muscles.
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PMID:A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart. 763 62

The spinal muscular atrophies (SMAs) are defined as a group of inherited disorders sharing the common pathological feature of degeneration of the anterior horn cells of the spinal cord and, in some cases, additionally of the bulbar motor nuclei. They are classified according to clinical features, including severity and distribution of muscle weakness and on their modes of inheritance. The SMAs are not uncommon: SMA type I (severe, acute infantile SMA) alone has a gene frequency in the UK estimated at 0.006. Together they represent a significant source of morbidity and mortality. Over the past 3 years, two major advances have been made towards understanding the molecular basis of these clinically heterogeneous disorders. First, in 1990, it was reported that all three forms of childhood-onset proximal SMA were linked to probes mapping to the proximal long arm of chromosome 5. Significant progress has been made towards isolating the gene or genes responsible, and a protocol for prenatal disease prediction in families with a previously severely affected child has been established. Second, in 1991, the molecular defect in adult-onset X-linked spinal and bulbar muscular atrophy was defined as an expansion of a (CAG)n trinucleotide repeat which encodes a string of glutamine residues in the first exon of the androgen receptor. Little progress has been made in elucidating the molecular pathology of the other SMAs. None of them has been linked to chromosome 5q markers, or indeed to markers elsewhere; the conditions are rare and pedigrees generally small. When the gene (or genes) on proximal 5q underlying SMA types I, II and III is cloned, mutations in this can then be sought in the other SMAs. The product of the chromosome 5q gene presumably plays a crucial role in maintaining the integrity of motor neurones, so determination of its structure and function may well have consequences far beyond those pertaining to the inherited SMAs. The identification of pathogenic mutations in the SOD-1 gene in familial amyotrophic lateral sclerosis is of great interest, although it is not clear that similar mechanisms contribute to the more common sporadic form of the disease.
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PMID:Disorders of the motor neurone. 795 56

Three genetic loci for the Charcot-Marie-Tooth (CMT) syndromes with slow motor nerve conduction velocities (hereditary motor and sensory neuropathy: HMSN type I) have been mapped to chromosomes 1 (CMT1B), 17 (CMT1A), and the X chromosome (CMTX). The clinical features of these three CMT subgroups are similar. To determine whether any clinical features distinguish CMTX families, the range of clinical findings and motor nerve conduction velocities were examined in two large CMTX families, the range of clinical findings and motor nerve conduction velocities were examined in two large CMTX families with CMTX proven by linkage to X-chromosome markers. CMTX males had more wasting and weakness than CMTX females or individuals with CMT1A. Patellar reflexes were more often retained in CMTX. Motor nerve conduction velocities were faster than in CMT1A. Intermediate-range median nerve conduction velocities were present in CMTX females (45 +/- 9 m/sec; range, 26 to 61 m/sec). These velocities were significantly faster than those for CMT1A females (22 +/- 8 m/sec, p < 0.0001). Median nerve conduction velocities in CMTX males (31 +/- 6 m/sec) were significantly slower than in CMTX females and faster than in CMT1A males (20 +/- 6 m/sec, p < 0.0001). The combination of slow conduction velocities in affected males (< 40 m/sec) and intermediate-range median motor conduction velocity results (> 40 m/sec) in affected or obligate carrier females is a useful distinguishing feature to separate CMTX from CMT1A, as intermediate conduction velocities are not present in autosomal-dominant dominant CMT1A families. This feature defines possible CMTX families for linkage studies. Families with no male-to-male inheritance of the syndrome, slow motor nerve conductions in affected males, and normal or intermediate-range conduction velocities in carrier females should be considered to be X-linked CMT families.
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PMID:Intermediate nerve conduction velocities define X-linked Charcot-Marie-Tooth neuropathy families. 825 57

A 36-year-old Russian man presented with neck and low back pain in September 1990. He was of normal stature, and there were no stigmata of rickets. The family history was negative for bone disease. He was found to have hypophosphatemia (2.3 mg/dl), impaired phosphate reabsorption (TmP/GFR 2.08), hyperphosphatasemia (254 IU/l), normocalcemia, normal vitamin D metabolite levels, and secondary hyperparathyroidism. Clinically, his spinal movements were quite impaired and there was moderate proximal muscle weakness. On skeletal radiographs, there was generalized osteosclerosis and multiple ligamentous calcifications. Transiliac biopsy was diagnostic for severe osteomalacia. He was treated with oral phosphate (240 mEq daily) and calcitriol (4 micrograms daily) with resultant very slow clinical, biochemical, and histomorphologic improvement. The patient had hypophosphatemic osteomalacia with some features of X-linked hypophosphatemia, but sporadic and of relatively late onset. The osteopenia, height loss, incapacitating weakness, and glycinuria that are characteristics of sporadic adult onset nonfamilial hypophosphatemia, with or without an associated tumor, and the low serum calcitriol levels that may be an additional characteristic of tumor-induced osteomalacia were absent. Other known causes of acquired renal tubular dysfunction were ruled out. The etiology, pathogenesis, and nosology of the disorder remain obscure, but treatment based on experience with other forms of hypophosphatemic osteomalacia was ultimately effective.
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PMID:A unique case of adult hypophosphatemic osteomalacia. 826 43

The neuronal forms of hereditary motor and sensory neuropathy (HMSN) are genetically heterogeneous with observed autosomal dominant, autosomal recessive and X-linked dominant inheritance. All three forms are characterized by degeneration of select populations of motor and sensory neurons with accompanying atrophy and degeneration of their axons. Large calibre myelinated fibres are predominantly affected and fibre degeneration and fibre loss progresses from distally to proximally. Attempts of regeneration are noted in all except the severe childhood form. The clinical picture is that of peroneal and distal leg muscle wasting and weakness, distal sensory loss and areflexia. Hand muscles may be severely affected in the autosomal recessive and X-linked dominant forms. Motor and sensory nerve conduction velocities are only moderately slowed and evoked maximum compound motor and sensory amplitudes are reduced according to the degree of fibre loss. The gene locus remains unknown in both the autosomal dominant and autosomal recessive types. For the X-linked dominant HMSN, the gene locus has been mapped closely by linkage analysis to DNA loci in the pericentromeric region of the X-chromosome.
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PMID:Hereditary motor and sensory neuropathy: HMSN type II (neuronal type) and X-linked HMSN. 829 76

Two cases of X-linked bulbo-spinal muscular atrophy and one sporadic case with the same clinical features are presented. All three cases were extensively studied by electrophysiological methods. One of the patients showed some transient weakness, which was partly improved by pyridostigmin. In this patient the Decrement test and jitter revealed a mild degree of motor-end plate dysfunction. Clinical and electrophysiological findings obtained from all three patients suggest that in Kennedy syndrome cell bodies of group IA muscle afferents are also affected selectively, with other peripheral afferents.
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PMID:X-linked bulbospinal muscular atrophy (Kennedy's syndrome): a report of three cases. 842 13

The dystrophin-deficient, X-linked dystrophic mouse (mdx) was used to evaluate the efficacy of prednisolone treatment. A test protocol was used to take advantage of the quantifiable weakness and disability as well as molecular genetic defect shared with the X-linked Duchenne muscular dystrophy (DMD). Whole-body weakness and fatigue were determined by non-invasive force-transducer physiographic and variable-speed treadmill techniques, respectively. Other measurements included hind-limb muscle protein, calcium, and histomorphology. Subcutaneously-administered prednisolone elicited significant improvements in whole body strength throughout a two-month test period. Increases in strength were also accompanied by measurable increments in running endurance. In fact, prednisolone treatment appeared to protect mdx mice from the stressful effect of continuous running as determined by strength and muscle fiber diameter. Test results from this study support the limited therapeutic benefit observed previously in DMD patients treated with the glucocorticoid.
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PMID:Strength and endurance in the therapeutic evaluation of prednisolone-treated MDX mice. 843 32


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