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1.
BMJ Case Rep ; 14(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811091

RESUMO

We report a case of a 55-year-old man presenting with diplopia, masticatory weakness and dysarthria several weeks post multitrauma. The clinical suspicion of myasthenia gravis (MG) was supported with positive acetylcholine receptor antibodies and abnormal repetitive stimulation study. He responded well to pyridostigmine, intravenous immunoglobulin and oral prednisolone. In this report, we describe the timing and progression of MG in our patient, and review the literature pertaining to the relationship between trauma and MG. The search for definitive evidence of causation may be impractical, but should not delay the recognition and management of a treatable condition.


Assuntos
Blefaroptose , Miastenia Gravis , Diplopia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Prednisolona/uso terapêutico , Brometo de Piridostigmina/uso terapêutico , Ferimentos e Lesões/complicações
3.
BMC Infect Dis ; 20(1): 765, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066761

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. METHODS: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. DISCUSSION: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).


Assuntos
Inibidores da Colinesterase/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Brometo de Piridostigmina/uso terapêutico , Adulto , Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Humanos , Inflamação , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Respiração Artificial
8.
Medicine (Baltimore) ; 99(15): e19781, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282741

RESUMO

INTRODUCTION: Surgical stress and pain are potential provoking factors for postoperative myasthenic crisis (POMC). We report the occurrence of early POMC and late deep vein thrombosis (DVT) in a man with myasthenia gravis (MG) undergoing thymectomy, addressing possible link between reversal of opioid overdose with naloxone and the triggering of POMC. PATIENT CONCERNS: A 71-year-old man with impaired renal function (ie, estimated glomerular filtration rate [egfr]: 49.1 mL/min/1.73 m) with diagnosis of MG made 2 months ago was scheduled for thymectomy. After uncomplicated surgery, he experienced opioid overdose that was treated with naloxone. Hyperlactatemia then developed with a concomitant episode of hypertension. Three hours after reversal, he suffered from myasthenic crisis presenting with respiratory failure and difficult weaning from mechanical ventilation. DIAGNOSIS: Stress-induced hyperlactatemia and subsequent myasthenic crisis INTERVENTIONS:: Pyridostigmine and immunosuppressive therapy with prednisolone were initiated. Hyperlactatemia subsided on postoperative day (POD) 5. Tracheal extubation was performed successfully on POD 6. OUTCOMES: During the course of hospitalization, his eGFR (ie, 88.9 mL/min/1.73 m) was found to improve postoperatively. After discharge from hospital, he developed DVT in the left femoral and popliteal veins on POD 24 when he was readmitted for immediate treatment with low-molecular-weight heparin. He was discharged without sequelae on POD 31. There was no recurrence of myasthenic crisis or DVT at 3-month follow-up. CONCLUSIONS: Following naloxone administration, hyperlactatemia may be an indicator of pain-related stress response, which is a potential provoking factor for myasthenic crisis. Additionally, patients with MG may have an increased risk of DVT possibly attributable to immune-mediated inflammation. These findings highlight the importance of perioperative avoidance of provoking factors including monitoring of stress-induced elevations in serum lactate concentration, close postoperative surveying for myasthenic crisis, and early recognition of possible thromboembolic complications in this patient population.


Assuntos
Miastenia Gravis/complicações , Timectomia/efeitos adversos , Trombose Venosa/etiologia , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hiperlactatemia/induzido quimicamente , Hiperlactatemia/diagnóstico , Hiperlactatemia/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Miastenia Gravis/diagnóstico , Miastenia Gravis/cirurgia , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Brometo de Piridostigmina/administração & dosagem , Brometo de Piridostigmina/uso terapêutico , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Resultado do Tratamento
9.
Arq Neuropsiquiatr ; 78(3): 179-181, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32215460

RESUMO

Currently, pyridostigmine bromide is an indispensable anticholinesterase agent used worldwide to treat patients with Myasthenia Gravis (MG). However, pyridostigmine bromide was unsuccessful in its "pioneering trials" to treat a series of MG patients. There are important historical landmarks before pyridostigmine bromide becomes useful, safe and indispensable for MG therapy. After 70 years of these "pioneering trials", this article reviews some historical aspects related to them, as well as other preliminary trials using pyridostigmine bromide as therapy for MG patients.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Brometo de Piridostigmina/uso terapêutico , Humanos
10.
Arq. neuropsiquiatr ; 78(3): 179-181, Mar. 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1098074

RESUMO

Abstract Currently, pyridostigmine bromide is an indispensable anticholinesterase agent used worldwide to treat patients with Myasthenia Gravis (MG). However, pyridostigmine bromide was unsuccessful in its "pioneering trials" to treat a series of MG patients. There are important historical landmarks before pyridostigmine bromide becomes useful, safe and indispensable for MG therapy. After 70 years of these "pioneering trials", this article reviews some historical aspects related to them, as well as other preliminary trials using pyridostigmine bromide as therapy for MG patients.


Resumo Atualmente, o brometo de piridostigmina é um indispensável agente anticolinesterásico usado em todo o mundo no tratamento de pacientes com Miastenia Gravis (MG). Contudo, o brometo de piridostigmina não foi bem-sucedido, em seus "ensaios clínicos pioneiros", no tratamento de uma série de pacientes com MG. Existem importantes marcos históricos antes do brometo de piridostigmina se tornar útil, seguro e indispensável no tratamento da MG. Após 70 anos desses "ensaios clínicos pioneiros", este artigo revisa alguns aspectos históricos a eles relacionados, bem como a outros estudos preliminares que usaram o brometo de piridostigmina como um tratamento para pacientes com MG.


Assuntos
Humanos , Brometo de Piridostigmina/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Miastenia Gravis/tratamento farmacológico
11.
Trop Doct ; 50(3): 238-239, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31902297

RESUMO

A 30-year-old woman presented as an emergency with a history of snakebite 5 h previously with signs of bulbar palsy, ptosis, respiratory distress and weakness of all four limbs. Mechanical ventilation, anti-snake venom (ASV) and supportive management were immediately instituted. With the third dose of ASV, an early anaphylactic reaction ensued. Subsequent management with corticosteroids and antihistamines over the next few days allowed consciousness to return but muscle power did not improve beyond 2/5. A trial of intravenous neostigmine with glycopyrrolate, however, improved motor power in all four limbs to 3/5. Oral pyridostigmine at 60 mg every 8 h allowed subsequent full motor recovery in all four extremities. We suggest consideration of pyridostigmine to promote motor recovery after an allergic reaction to ASV.


Assuntos
Anafilaxia/induzido quimicamente , Antivenenos/uso terapêutico , Brometo de Piridostigmina/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Serpentes/antagonistas & inibidores , Adulto , Antivenenos/efeitos adversos , Feminino , Humanos , Paralisia/tratamento farmacológico , Paralisia/fisiopatologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Mordeduras de Serpentes/fisiopatologia
12.
BMJ Case Rep ; 12(12)2019 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-31818887

RESUMO

A 24-year-old otherwise healthy male presented to us with unilateral ptosis and contralateral lid retraction with limitation of extraocular movements; the disease had a gradual chronic course, which raised a suspicion of ocular myasthenia. Ice pack test was performed, which improved the ptosis; further investigations confirmed the diagnosis of ocular myasthenia. Patient was started on pyridostigmine and oral prednisolone which improved the extraocular movements and ptosis.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Oftalmopatias/diagnóstico , Miastenia Gravis/diagnóstico , Blefaroptose/etiologia , Inibidores da Colinesterase/uso terapêutico , Temperatura Baixa , Diagnóstico Diferencial , Oftalmopatias/tratamento farmacológico , Movimentos Oculares , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Miastenia Gravis/tratamento farmacológico , Prednisolona/uso terapêutico , Brometo de Piridostigmina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
13.
Medicine (Baltimore) ; 98(52): e18406, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31876713

RESUMO

As an anesthetic reversal agent, there are concerns with cholinesterase inhibitors regarding worsening of Parkinson's disease (PD)-related symptoms. Sugammadex, a relatively new reversal agent, does not inhibit acetylcholinesterase and does not require co-administration of an antimuscarinic agent. The present study compared the recovery profiles of 2 agents initially administered for reversal of neuromuscular blockade in patients with advanced PD who underwent deep brain stimulator implantation.A total of 121 patients with PD who underwent deep brain stimulator implantation were retrospectively analyzed. Patients were divided into 1 of 2 groups according to the type of neuromuscular blockade reversal agent (pyridostigmine vs sugammadex) initially administered. Recovery profiles reflecting time to extubation, reversal failure at first attempt, and hemodynamic stability, including incidence of hypertension or tachycardia during the emergence period, were compared.Time to extubation in the sugammadex group was significantly shorter (P < .001). In the sugammadex group, reversal failure at first attempt did not occur in any patient, while it occurred in seven (9.7%) patients in the pyridostigmine group (P = .064), necessitating an additional dose of pyridostigmine (n = 3) or sugammadex (n = 4). The incidence of hemodynamic instability during anesthetic emergence was significantly lower in the sugammadex group than in the pyridostigmine group (P = .019).Sugammadex yielded a recovery profile superior to that of pyridostigmine during the anesthesia emergence period in advanced PD patients. Sugammadex is also likely to be associated with fewer adverse effects than traditional reversal agents, which in turn would also improve overall postoperative management in this patient population.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Estimulação Encefálica Profunda , Eletrodos Implantados , Bloqueio Neuromuscular/métodos , Doença de Parkinson/terapia , Implantação de Prótese , Brometo de Piridostigmina/uso terapêutico , Sugammadex/uso terapêutico , Período de Recuperação da Anestesia , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Neuromuscular/efeitos adversos , Implantação de Prótese/métodos , Estudos Retrospectivos
14.
Heart Surg Forum ; 22(5): E340-E342, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31596708

RESUMO

Patients diagnosed with ocular myasthenia gravis (MG) and mitral valve disease represent a significant perioperative management problem, especially for the anaesthesiologist, due to complex inter-actions between the disease, drugs to treat the disease, and anaesthetic agents, such as neuromuscu-lar blocking agents (NMBAs). This paper describes the successful management of a 31-year-old female with mitral valve stenosis and ocular MG who was diagnosed with MG 4 years prior to the indication for cardiac surgery. Preoperatively, the patient was under treatment with Pyridostigmine and Prednisone. Mitral valve replacement and full thymectomy were performed, under general anaesthesia, using Fentanyl, Sevoflurane and low doses of non-depolarising NMBAs. The postoperative course was uneventful, the patient was extubated at 6 hours postoperatively, in-tensive care unit stay was 48 hours, and the patient was discharged after 6 days without any compli-cations. After 3 months, at the follow-up examination, the patient's ocular symptoms (eyelid ptosis) disappeared.


Assuntos
Implante de Prótese de Valva Cardíaca/métodos , Estenose da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Miastenia Gravis/cirurgia , Timectomia , Adulto , Anestésicos Combinados , Anti-Inflamatórios/uso terapêutico , Interações Medicamentosas , Feminino , Fentanila , Humanos , Estenose da Valva Mitral/complicações , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Prednisona/uso terapêutico , Brometo de Piridostigmina/uso terapêutico , Sevoflurano
15.
Brain ; 142(12): 3713-3727, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633155

RESUMO

Acetylcholine receptor deficiency is the most common form of the congenital myasthenic syndromes, a heterogeneous collection of genetic disorders of neuromuscular transmission characterized by fatiguable muscle weakness. Most patients with acetylcholine receptor deficiency respond well to acetylcholinesterase inhibitors; however, in some cases the efficacy of acetylcholinesterase inhibitors diminishes over time. Patients with acetylcholine receptor deficiency can also benefit from the addition of a ß2-adrenergic receptor agonist to their medication. The working mechanism of ß2-adrenergic agonists in myasthenic patients is not fully understood. Here, we report the long-term follow-up for the addition of ß2-adrenergic agonists for a cohort of patients with acetylcholine receptor deficiency on anticholinesterase medication that demonstrates a sustained quantitative improvement. Coincidently we used a disease model to mirror the treatment of acetylcholine receptor deficiency, and demonstrate improved muscle fatigue, improved neuromuscular transmission and improved synaptic structure resulting from the addition of the ß2-adrenergic agonist salbutamol to the anticholinesterase medication pyridostigmine. Following an initial improvement in muscle fatiguability, a gradual decline in the effect of pyridostigmine was observed in mice treated with pyridostigmine alone (P < 0.001). Combination therapy with pyridostigmine and salbutamol counteracted this decline (P < 0.001). Studies of compound muscle action potential decrement at high nerve stimulation frequencies (P < 0.05) and miniature end-plate potential amplitude analysis (P < 0.01) showed an improvement in mice following combination therapy, compared to pyridostigmine monotherapy. Pyridostigmine alone reduced postsynaptic areas (P < 0.001) and postsynaptic folding (P < 0.01). Combination therapy increased postsynaptic area (P < 0.001) and promoted the formation of postsynaptic junctional folds (P < 0.001), in particular in fast-twitch muscles. In conclusion, we demonstrate for the first time how the improvement seen in patients from adding salbutamol to their medication can be explained in an experimental model of acetylcholine receptor deficiency, the most common form of congenital myasthenic syndrome. Salbutamol enhances neuromuscular junction synaptic structure by counteracting the detrimental effects of long-term acetylcholinesterase inhibitors on the postsynaptic neuromuscular junction. The results have implications for both autoimmune and genetic myasthenias where anticholinesterase medication is a standard treatment.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Albuterol/farmacologia , Inibidores da Colinesterase/uso terapêutico , Síndromes Miastênicas Congênitas/tratamento farmacológico , Junção Neuromuscular/efeitos dos fármacos , Brometo de Piridostigmina/uso terapêutico , Potenciais de Ação/fisiologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Albuterol/uso terapêutico , Animais , Inibidores da Colinesterase/farmacologia , Modelos Animais de Doenças , Humanos , Camundongos , Brometo de Piridostigmina/farmacologia , Transmissão Sináptica/efeitos dos fármacos
16.
Muscle Nerve ; 60(6): 707-715, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31487038

RESUMO

INTRODUCTION: The Myasthenia Gravis Patient Registry (MGR) is a voluntary, patient-submitted database dedicated to improve understanding of care/burden of myasthenia gravis (MG). METHODS: In this study we present analyses of baseline records through July 2017 (n = 1140) containing data on the MG-Activities of Daily Living (MG-ADL) and the MG 15-item Quality of Life (MG-QOL15) instruments, two validated scales assessing quality of life in MG patients at sign-up into the MGR. RESULTS: Most registrants reported moderate to severe impairment of health-related quality of life, with a median MG-ADL score of 6 and a median MG-QOL15 score of 21. Seventy-one percent of the patients had received pyridostigmine. Corticosteroids, mycophenolate mofetil, and azathioprine were the most common immunomodulators/immunosuppressants, with 85% of participants having ever using one of these agents. Forty-seven registrants reported receiving intravenous immunoglobulin, and 30% received plasma exchange. Twelve percent reported other treatments, and 40% were unsure whether they received less common therapies. Forty percent had undergone thymectomy. DISCUSSION: The MGR data correlate well with other MG cohorts. Many MG patients remain negatively impacted despite treatment.


Assuntos
Atividades Cotidianas , Inibidores da Colinesterase/uso terapêutico , Imunossupressores/uso terapêutico , Miastenia Gravis/fisiopatologia , Miastenia Gravis/terapia , Qualidade de Vida , Corticosteroides/uso terapêutico , Adulto , Idoso , Azatioprina/uso terapêutico , Estudos Transversais , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Troca Plasmática/métodos , Brometo de Piridostigmina/uso terapêutico , Sistema de Registros
18.
Neuromuscul Disord ; 29(9): 664-670, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31488385

RESUMO

The distribution of muscle weakness in myasthenia gravis (MG) patients with acetylcholine receptor (AChR) antibodies is highly variable. As muscle groups respond differently to therapeutic interventions, it is important to acknowledge this variability. We analysed the distribution of muscle weakness in 225 AChR MG patients over time. On the basis of combinations of muscle weakness, seven phenotypes were defined: 'ocular' (O), 'bulbar' (B), 'neck/limbs/respiratory' (NLR), or a combination (O+B, O+NLR, B+NLR and O+B+NLR). MG remained restricted to ocular weakness in 5%, whereas 7% never had ocular weakness. At last follow-up, ocular or bulbar weakness had resolved more frequently than NLR weakness (40%, 38% and 25%; p = 0.003, respectively). Patients with O, B or OB phenotype at baseline had a higher age at onset and were more frequently male than patients with NLR, ONLR, BNLR or OBNLR phenotype (52.7 ±â€¯17.5 vs. 44.0 ±â€¯18.9; p = 0.007 and 64% vs. 37%; p = 0.002, respectively). MG patients have heterogeneous distributions of muscle weakness and frequently shift between phenotypes. The phenotypic variations found in AChR MG suggest that also other factors aside from the AChR antibody mediated immune response are of importance in determining the disease expression in MG.


Assuntos
Músculos da Mastigação/fisiopatologia , Debilidade Muscular/fisiopatologia , Miastenia Gravis/fisiopatologia , Músculos do Pescoço/fisiopatologia , Músculos Oculomotores/fisiopatologia , Músculos Faríngeos/fisiopatologia , Músculos Respiratórios/fisiopatologia , Adulto , Idade de Início , Idoso , Blefaroptose/etiologia , Blefaroptose/fisiopatologia , Inibidores da Colinesterase/uso terapêutico , Estudos de Coortes , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Diplopia/etiologia , Diplopia/fisiopatologia , Progressão da Doença , Disartria/etiologia , Disartria/fisiopatologia , Extremidades , Músculos Faciais/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Mastigação , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Músculo Esquelético/fisiopatologia , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Fenótipo , Prednisona/uso terapêutico , Estudos Prospectivos , Brometo de Piridostigmina/uso terapêutico
19.
Ann N Y Acad Sci ; 1452(1): 18-33, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31393614

RESUMO

Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell dependence and complement involvement. Cholinesterase inhibitors (e.g., pyridostigmine bromide), glucocorticoids, and azathioprine are currently recommended as first-line treatments for MG, though they have limitations, including potential toxicity and ineffectiveness in patients with refractory MG. In recent years, owing to an increasing understanding of MG pathogenesis the development and execution of clinical trials with novel biologics, including monoclonal antibodies (mAbs) that have demonstrated higher safety and more specificity, provide new opportunities for the treatment of MG. In this article, we review recent advances in MG pathogenesis and the mAbs that have been used for target-specific MG therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Miastenia Gravis/tratamento farmacológico , Azatioprina/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Miastenia Gravis/imunologia , Brometo de Piridostigmina/uso terapêutico , Resultado do Tratamento
20.
Neuromuscul Disord ; 29(7): 549-553, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31255525

RESUMO

Limb-girdle myasthenia with tubular aggregates, a subtype of congenital myasthenic syndrome, is an extremely rare autosomal recessive genetic disease characterized by prominent limb-girdle weakness and good response to acetylcholinesterase inhibitor therapy. Herein, we reported two novel mutations of GFPT1 gene in a Chinese pedigree. Two siblings presented with fatigue, weakness of limb-girdle and decrement of the muscle action potential with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but anti-AChR antibodies were negative. Two novel missense mutations (p.Lys154Asn and p.Asn363Ser) in GFPT1 were identified through genetic testing conducted on 167 well-established genes associated with muscular diseases by targeted high throughput sequencing. Both mutations have not been recorded in the dsSNP database, Exome Aggregation Consortium database and 1000 Genomes Project database. The mutation sites were co-segregated with the phenotype and conserved between the different species. The mutations were not found in the 200 unrelated normal controls. Muscle biopsies revealed tubular aggregates, in accordance with previous reports with GFPT1 mutations. Subsequently, dramatic improvement in strength occurred following anti-cholinesterase therapy. Our study will be helpful for the diagnosis and treatment for Limb-girdle myasthenia with tubular aggregates.


Assuntos
Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação de Sentido Incorreto/genética , Miopatias Congênitas Estruturais/genética , Potenciais de Ação , Animais , Grupo com Ancestrais do Continente Asiático , Inibidores da Colinesterase/uso terapêutico , Bases de Dados Genéticas , Estimulação Elétrica , Feminino , Testes Genéticos , Humanos , Masculino , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/tratamento farmacológico , Distrofia Muscular do Cíngulo dos Membros/patologia , Miopatias Congênitas Estruturais/tratamento farmacológico , Miopatias Congênitas Estruturais/patologia , Linhagem , Polimorfismo de Nucleotídeo Único , Brometo de Piridostigmina/uso terapêutico , Adulto Jovem
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