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

Sixty-six individuals with Limb-Girdle Syndrome (LGS) were evaluated over a 10-yr period and classified into three types: 19 severe autosomal recessive muscular dystrophy of childhood (ARMDC), alternatively referred to by some as SCARMD, 18 autosomal dominant late onset (ADLO), and 29 pelvifemoral (PF) individuals. ARMDC subjects showed the greatest weakness, 2.5 +/- 1.0, mean Manual Muscle Test (MMT) grade for all muscles combined, and the only significant progression of loss of strength, -0.59 MMT unit decline per decade. Strength loss in ADLO and PF types was about the same, 3.7 +/- 0.7 and 4.0 +/- 0.7 grades, respectively. Quantitative strength measurements in ADLO and PF types were more sensitive than MMTs, showing losses of 30-40% strength in muscle groups with MMT grades of 4 or higher. All three types showed greater proximal and lower extremity weakness but usually no difference between flexor and extensor strength. There was a high percentage (44%) of mild very slowly progressive scoliosis in ARMDC, but spine deformity was unusual in ADLO and PF (11%) LGS. Contractures were few, slowly progressive, and usually mild in severity in all types, although more frequent in ARMDC. There also was a low frequency of severe restrictive lung disease in all types (10%) but a high percentage of electrocardiogram abnormalities (62-73%). The most common electrocardiogram abnormalities were increased R/S ratio in V1 and infranodal conduction defects. Intellectual and cognitive functions were within normal limits. Mobility and extremity function reflected the strength differences between the ARMDC and other types of LGS. Eight-five percent of ARMDC individuals relied on a wheelchair for all or part of their mobility, and all were unable to complete timed motor performance tests within the 99th percentile range for controls.
 ...
PMID:Profiles of neuromuscular diseases. Limb-girdle syndromes. 757 19

In humans, mutations in the genes encoding components of the dystrophin-glycoprotein complex cause muscular dystrophy. Specifically, primary mutations in the genes encoding alpha-, beta-, gamma-, and delta-sarcoglycan have been identified in humans with limb-girdle muscular dystrophy. Mice lacking gamma-sarcoglycan develop progressive muscular dystrophy similar to human muscular dystrophy. Without gamma-sarcoglycan, beta- and delta-sarcoglycan are unstable at the muscle membrane and alpha-sarcoglycan is severely reduced. The expression and localization of dystrophin, dystroglycan, and laminin-alpha2, a mechanical link between the actin cytoskeleton and the extracellular matrix, appears unaffected by the loss of sarcoglycan. We assessed the functional integrity of this mechanical link and found that isolated muscles lacking gamma-sarcoglycan showed normal resistance to mechanical strain induced by eccentric muscle contraction. Sarcoglycan-deficient muscles also showed normal peak isometric and tetanic force generation. Furthermore, there was no evidence for contraction-induced injury in mice lacking gamma-sarcoglycan that were subjected to an extended, rigorous exercise regimen. These data demonstrate that mechanical weakness and contraction-induced muscle injury are not required for muscle degeneration and the dystrophic process. Thus, a nonmechanical mechanism, perhaps involving some unknown signaling function, likely is responsible for muscular dystrophy where sarcoglycan is deficient.
 ...
PMID:Muscle degeneration without mechanical injury in sarcoglycan deficiency. 1048 93

All dystrophin-associated proteins contain sarcoglycan complex. Different forms of muscular dystrophy are caused by defective expression of different proteins of this structure. gamma-Sarcoglycan deficiency muscular dystrophy, so-called severe childhood autosomal recessive muscular dystrophy (SCARMD), is a rare disease that has not been previously reported in Taiwan. This paper describes two Taiwanese adults with this disease: a 26-year-old man with calf pseudohypertrophy who had weakness in both legs for 1 year; and a 43-year-old woman who had progressive weakness in all four limbs, with the initial symptom of gait disturbance at the age of 32 years. Analysis of muscle biopsy specimens, which showed total deficiency of gamma-sarcoglycan protein on immunostaining, confirmed the diagnosis of SCARMD in both cases. However, the clinical manifestations in these two patients, including lower proximal limb weakness initially developing in adulthood with a slow progressive course, are different from previously reported cases of SCARMD. The literature on this disease is reviewed and possible mechanisms of these distinct clinical presentations are discussed.
 ...
PMID:gamma-sarcoglycan deficiency muscular dystrophy in two adults. 1106 Oct 77

While calf muscle hypertrophy is a striking diagnostic finding in sarcoglycanopathy, as it is in Duchenne and Becker muscular dystrophies, its pathogenetic mechanism remains unknown. gamma-Sarcoglycan, one of the subunits of the sarcoglycan complex, is the protein responsible for gamma-sarcoglycanopathy. To elucidate the pathogenetic mechanisms of muscle hypertrophy and degeneration in muscular dystrophy, we utilized a mutant mouse as a model animal. In this study, we generated gamma-sarcoglycan-deficient (gsg-/-) mice by gene targeting. The gsg-/- mice described here, similar to the gsg-/- mice reported previously (J Cell Biol 142 (1998) 1279), demonstrated skeletal and cardiac muscle degeneration. The limb, shoulder, and pelvic muscles of the gsg-/- mice exhibited progressive muscle hypertrophy and weakness with age, and the findings were similar to those seen in other mouse models for limb-girdle and Duchenne muscular dystrophy. We found that the number of muscle fibers increased with age, and most of the fibers in the hypertrophic muscle were centrally nucleated regenerating fibers. Therefore, muscle hypertrophy of the gsg-/- mice may result from an increase of the number of muscle fibers and probable fiber branching and may not be due to the pseudohypertrophy caused by fibrous and fat tissue replacement, as has been long supposed in muscular dystrophy. The muscle pathology became more 'dystrophic' in mice over 1 year of age when there was a marked variation in fiber size with interstitial fibrosis.
 ...
PMID:Pathological analysis of muscle hypertrophy and degeneration in muscular dystrophy in gamma-sarcoglycan-deficient mice. 1260 1

Limb-girdle muscular dystrophy type 2C is an autosomal-recessive disorder caused by mutations in gamma-sarcoglycan encoding gene. This disease is characterized by childhood onset of progressive muscular dystrophy. Because of the clinical presentation, this disorder may be misdiagnosed as a dystrophinopathy. Two males (Patients A and B) from one Turkish family and one male (Patient C) from a Moroccan family had progressive walking disturbances for several years, exercise intolerance, and leg pains. Clinical examination revealed limb-girdle weakness and calf hypertrophy. Serum creatine kinase levels ranged from 1100 to 19000 U/L. The initial findings and course of the disease were less severe in Patient B compared with his brother (Patient A) at the same age. By means of immunohistochemistry on muscle biopsy all patients manifested reduced expression of alpha-, beta-, gamma-, and delta-sarcoglycans. DNA sequence analysis revealed a homozygous splice site mutation in exon 5 (IVS5+2T>C) in the Turkish family. In the patient from the Moroccan family a homozygous nonsense mutation in exon 2 (93G>A;Trp31X) was present. In conclusion, this report describes the clinical, histologic, and immunohistochemical characteristics of three children with limb-girdle muscular dystrophy type 2C. Two novel mutations in the gamma-sarcoglycan gene were present. We found phenotypic differences in two brothers.
 ...
PMID:Novel mutations in three patients with LGMD2C with phenotypic differences. 1508 11

Limb girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of primary myopathies involving progressive weakness and wasting of the muscles in the hip and shoulder girdles, with distal spread to the bulbar or respiratory musculature in rare cases. Depending on the mode of genetic transmission, six autosomal dominant forms (LGMD1A-F, 10-25%) and ten autosomal recessive forms (LGMD2A-J, 75-90%) are currently known. The prevalence of LGMDs is 0.8/100,000. These conditions are caused by mutations in genes encoding for myotilin (5q31, LGMD1A), lamin A/C (1q11-q21.2, LGMD1B), caveolin-3 (3p25, LGMD1C), unknown proteins (7q, LGMD1D, 6q23, LGMD1E, 7q32.1-32.2., LGMD1F), calpain-3 (15q15.1-21.1, LGMD2A), dysferlin (2p13.3-13.1, LGMD2B), gamma-sarcoglycan (13q12, LGMD2C), alpha-sarcoglycan, also known as adhalin (17q12-q21.3, LGMD2D), beta-sarcoglycan (4q12, LGMD2E), delta-sarcoglycan (5q33-q34, LGMD2F), telethonin (17q11-q12, LGMD2G), E3-ubiquitin ligase (9q31-q34.1, LGMD2H), fukutin-related protein (19q13.3, LGMD2I), and titin (2q31, LGMD2J). Cardiac involvement has been described for LGMD1B-E, LGMD2C-G, and LGMD2I. The time of onset varies between early childhood and middle age. There is no male or female preponderance. Disease progression and life expectancy vary widely, even among different members of the same family. The diagnosis is based primarily on DNA analysis. The history, clinical neurological examinations, blood chemistry investigations, electromyography, and muscle biopsy also provide information that is helpful for the diagnosis. No causal therapy is currently available.
 ...
PMID:[Limb girdle muscular dystrophies]. 1531 18

Episodic myoglobinuria is a well-recognized complication of metabolic myopathies, and may occur in Duchenne and Becker dystrophies, but has only rarely been associated with limb-girdle muscular dystrophy. We describe an unusual presentation, with rhabdomyolysis, of limb-girdle muscular dystrophy (LGMD). We evaluated a patient for progressive muscle weakness and tenderness, with myoglobinuria one week after initial presentation. Immunohistochemistry on muscle tissue revealed absent staining for gamma-sarcoglycan, confirmed by detection of a homozygous mutation in the gamma-sarcoglycan gene. Myoglobinuria has been previously reported only twice in LGMD. It is therefore important to recognize that myoglobinuria may be a symptom of a muscular dystrophy, and muscle biopsy and immunostaining are important tools for diagnosis.
 ...
PMID:Episodic myoglobinuria in a primary gamma-sarcoglycanopathy. 2035 42

Synovial sarcoma is a soft-tissue sarcoma. Its involvement of the spine is extremely rare. We report a 40 year old male who presented with shoulder pain and progressive weakness in all four limbs for six months with a visible, slowly growing bulge in his upper back. On examination he had quadriparesis and diffuse sensory deficit. MRI of the cervical spine showed a large soft tissue mass, iso to hypointense, extending into the neural canal, compressing the cord. The mass had a few internal areas of contrast enhancement with extension into the right paraspinal regions involving the vertebral bodies. Sub-periosteal spine dissection was done. Tumour was primarily extradural, involving and extending from paraspinal soft tissues to the posterior arches, laminae and spinous processes of the verteberae, with their destruction. Gross radical removal of the visible mass was done, followed by three cycles of radiation therapy. Excisional biopsy showed synovial sarcoma TYPE II. In conclusion, synovial sarcomas should be kept in the differentials of a mass arising in spinal axis.
 ...
PMID:Synovial sarcoma of cervicodorsal spine: A case report. 3031 11