Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical analysis of 378 acute cases of Malathion insecticide intoxication and pathological and histochemical investigation of skeletal muscles in 7 autopsied victims of acute poisoning have revealed the pronounced neuromuscular disorders. Generalized paresis and paralysis of muscles were observed in trunk and limbs. Muscular fasciculation, hypotonia and hyporeflexia were also generalized. Multiple foci of muscular fibers necrosis and necrobiosis were found with intermuscular nerves and motor endings degenerated, neuromuscular junctions cholinesterase sharply inactivated.
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PMID:[Clinico-morphologic and histochemical changes in the neuromuscular apparatus in acute carbophos poisoning]. 318 79

Three sisters with myopathy characterized by different degrees of weakness, hypotonia, cramps and a significant hypertrophy of the calves underwent clinical tests. Laboratory examinations (nerve conduction velocity, electromyography and serum enzymes), serial histochemical analyses of muscle specimens and tests for muscular acetylcholinesterase (AChE) activity and its molecular forms were performed. AChE activities did not differ significantly from those of controls, while sedimentation patterns evidenced the disappearance of 16 S, 13 S and 10 S molecular forms in the elder sisters. The genealogical tree of the patients is described and their cases compared to those of others with calf hypertrophy reported in the literature.
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PMID:Muscle acetylcholinesterase in a familial myopathic disease. 362 73

Forty children with hypotonia and non progressive cerebral impairment were observed. In all cases muscle morpho-histometric and ultrastructural studies were performed, in 13 cases muscular acetylcholinesterase study was carried out. The Authors pointed out the high frequency (92% of cases) of muscle abnormalities: histochemical alteration of fibre type distribution (type 1 or type 2 fibres prevalence, type 2C persistence), diameter change (hypertrophy or hypotrophy of the fibres). In 37.5% of the cases, randomly distributed, were also present myofibrillar degeneration, Z band streaming, desalignment or marked destructuration of the sarcomeres. The muscular acetylcholinesterase study showed the same anomalous pattern of molecular forms (11 out of 13 cases), with increase of light (6S, 4S) and disappearance of heavy (16S) and medium forms (13S, 10S), without significant change of enzymatic activity. The possible alterated influence of CNS on muscle fibre differentiation and growth because of abnormal neural control is discussed. This hypothesis even if could be related with abnormal fibre typing and diameter, do not seem to explain the ultrastructural and biochemical abnormalities observed.
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PMID:Muscular abnormalities in children with muscular hypotonia and cerebral damage. 368 84

A term infant required intubation for respiratory depression. Examination revealed hypotonia and areflexia with intact extraocular movements. Electrodiagnostic studies demonstrated defective neuromuscular transmission characterized by borderline low motor evoked amplitudes, profound decremental responses at all stimulation rates, and moderate facilitation (50 to 740%) 15 seconds after 5 seconds of 50 Hz stimulation. Repetitive muscle action potential responses were not recorded following stimulation of nerves by single shocks. Sensory evoked responses and needle electromyographic findings were normal, as were acetylcholine receptor antibody levels. Results of muscle histochemical analyses, including acetylcholinesterase stains, were normal. End-plate histometric analyses demonstrated only a slight reduction in mean synaptic vesicle diameter compared with that in an adult control subject. In vitro muscle contractile properties, stimulating the muscle directly, were normal. Anticholinesterase medications were ineffective. Guanidine produced clinical deterioration. The amplitude of motor evoked responses progressively declined, whereas the percentage of decrement and amount of post-tetanic facilitation increased. Although the nature of the transmission defect was not identified, the data are consistent with abnormal acetylcholine resynthesis, mobilization, or storage without abnormality of release or receptors.
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PMID:Abnormal neuromuscular transmission in an infantile myasthenic syndrome. 608 19

Authors present some of their results from an epidemiological study on the effect of fenitrothion (Metation EK-50) on the organism of occupationally exposed workers in the production of this preparation and in female workers in the packing room during a 5-year period. The results of clinical examinations pointed to parasympathetic stimulation and disposition to hypotonia. Neurological and psychiatric findings revealed a low-grade pseudoneurasthenic syndrome in 33% of females and in 15% of males. The results of psychodiagnostic tests after the exposure to fenitrothion and its intermediate products showed partial deterioration of retention, impairment of visuomotor coordination of movements in tapping and that or orientation readiness, prolonged average time of decision-making and prolonged average reaction time for complex sensorimotor responses. From among the biochemical parameters after the exposure to fenitrothion the following ones can be mentioned: inhibition of cholinesterase in blood, increase of GPT transaminase, increase of insoenzyme LDH5 and changes in protein fractions, as statistically significant (P less than 0,001). The values of excreted p-nitro-m-cresol (NC) in urine in males after the exposure to fenitrothion were 5,61 mg/l on the average, compared with the average value of 1,54 mg NC/l before exposure. The average values of excreted NC in urine in females involved in bottling Metation were those of 4,0 mg NC or 6,58 mg NC/l of urine after exposure. The concentration of fenitrotrion in the air of the working space ranged from 0,028 to 0,118 mg X m-3. From the values of the excreted NC in urine in the exposed workers and in volunteers, to whom fenitrothion was administered in the doses of 2,5 to 20 mg, it can be judged that the organism of exposed workers received approximately 15 mg of fenitrothion per capita a day and those of exposed females 20 mg or more per capita a day.
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PMID:Clinical and laboratory findings in Metation EK-50. 681 74

Two children, now 5 1/2 and 6 years of age, presented as neonates with hypotonia, multiple joint contractures, ptosis, extraocular weakness, bulbar symptoms, and respiratory distress. Fluctuations and episodic exacerbations of weakness necessitated respiratory support. Both children are developmentally delayed and cannot walk independently, although one child underwent bilateral tenotomies. Biochemical investigations and electromyography, including slow-rate, repetitive nerve stimulation, were normal. Acetylcholine receptor antibodies in serum were absent. Single-fiber electromyography with axonal stimulation revealed prolonged mean jitter in the tibialis anterior and extensor digitorum muscles, with more than 2 abnormal individual jitter values in each muscle. Muscle biopsy demonstrated normal pattern and morphology of muscle fibers; immunohistochemical staining for cholinesterase was positive. Electron microscopy revealed abnormalities in motor endplates: atrophy, flattening of primary synaptic clefts, and paucity of side branches. These findings represent one of the postsynaptic abnormalities (i.e., acetylcholine receptor deficiency or paucity of synaptic folds). Both children improved clinically on pyridostigmine therapy. Arthrogryposis congenital multiplex due to congenital myasthenic syndrome, as diagnosed in our patients, has been reported once before. The diagnosis can be established by clinical history, neurologic examination, and electrophysiologic and pathologic findings. Clinical improvement can be achieved with high-dose anticholinesterase therapy.
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PMID:Arthrogryposis multiplex congenita due to congenital myasthenic syndrome. 761 91

A rural-area resident male patient deliberately ingested chlorpiriphos, an organophosphate insecticide. Although presented with cholinergic symptoms initially, he suffered general condition deterioration after 4 d characterized by muscular weakness, hypotonia, arreflexia and recumbent dyspnea requiring ventilatory support. These clinical manifestations occur from liposoluble organophosphates or metabolites with long-lasting half time, causeing delayed inhibition of acetylcholinesterase and subsequent burn out of the neuromuscular junction from acetylcholine overstimulation.
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PMID:Intermediate syndrome secondary to ingestion of chlorpiriphos. 1120 75

Congenital myasthenic syndrome (CMS) is a heterogeneous group of inherited disorder which does not associate with anti-acetylcholine receptor (AChR) antibody. The presence of AChR autoantibody is pathogenic and highly sensitive and specific for autoimmune myasthenia gravis (MG). We describe 2 children from unrelated families who presented with hypotonia, ptosis and fatigability in early infancy with anti-AChR antibodies detected via ELISA on 2 separate occasions in the sera. Both were treated as refractory autoimmune MG due to poor clinical response to acetylcholinesterase inhibitor and immunotherapy. In view of the atypical clinical features, genetic studies of CMS were performed and both were confirmed to have novel pathogenic mutations in the COLQ gene. To the best of our knowledge, the presence of anti-AChR antibody in COLQ-related CMS has never been reported in the literature. The clinical presentation of early onset phenotype, and refractoriness to acetylcholinesterase inhibitor and immunotherapy should prompt CMS as a differential diagnosis.
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PMID:Congenital myasthenic syndrome with novel pathogenic variants in the COLQ gene associated with the presence of antibodies to acetylcholine receptors. 3183 Dec 53

Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin-2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS-disease gene and expands its clinical and genetic spectrum to include recessive loss-of-function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications.
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PMID:Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome. 3277 97