RESUMO
Forty percent to 50% of acetylcholine receptor antibody-seronegative patients with myasthenia gravis have muscle-specific receptor tyrosine kinase antibodies. Many muscle-specific receptor tyrosine kinase + myasthenia gravis patients remain refractory with conventional therapies. Rituximab is an anti-CD20 monoclonal antibody used in refractory B-cell disorders. Currently there is no standard dosing schedule for rituximab. We present two muscle-specific receptor tyrosine kinase + myasthenia gravis patients clinically refractory to conventional therapy who, after a single course of rituximab, became asymptomatic and discontinued all medication.
Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Autoanticorpos/biossíntese , Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Adolescente , Adulto , Anticorpos Monoclonais Murinos/efeitos adversos , Resistência a Medicamentos/imunologia , Feminino , Humanos , Miastenia Gravis/enzimologia , Recuperação de Função Fisiológica/imunologia , Rituximab , Tempo , Resultado do TratamentoRESUMO
Autosomal inherited mitochondrial diseases have been of increasing interest among clinicians and mitochondrial research groups because these diseases are caused through a secondary effect on the mitochondrial DNA. It was thought that the genetic stability of mitochondrial DNA relies on the accuracy of DNA polymerase gamma. Mutations of DNA polymerase gamma 1 gene (MIM# 174763) have been shown to be a cause of mitochondrial disorders associated with Mendelian disorders characterized by multiple mitochondrial DNA deletions or depletions. To date, several clinical phenotypes associated with polymerase gamma mutation have been reported presenting in both adults and children. We present 3 children in whom were found to have reported pathogenic DNA polymerase gamma 1 mutations: heterozygous p.G517V in 2 half siblings and heterozygous p.T251I and p.P587L in the other. The aim of this communication is to report 3 pediatric cases associated with DNA polymerase gamma 1 mutations to augment the expanding clinical phenotype that has been previously reported.
Assuntos
DNA Polimerase Dirigida por DNA/genética , Predisposição Genética para Doença/genética , Doenças Mitocondriais/enzimologia , Doenças Mitocondriais/genética , Mutação/genética , Criança , Pré-Escolar , Transtornos Cromossômicos/genética , Análise Mutacional de DNA , DNA Polimerase gama , DNA Mitocondrial/genética , Deficiências do Desenvolvimento/enzimologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Epilepsia/enzimologia , Epilepsia/genética , Epilepsia/fisiopatologia , Marcadores Genéticos/genética , Genótipo , Humanos , Lactente , Padrões de Herança/genética , Masculino , Doenças Mitocondriais/fisiopatologia , Mioclonia/enzimologia , Mioclonia/genética , Mioclonia/fisiopatologia , Fenótipo , Valor Preditivo dos Testes , PrognósticoRESUMO
Danon disease is an X-linked cardioskeletal myopathy, originally reported as "lysosomal glycogen storage disease with normal acid maltase," resulting from a primary deficiency of lysosome-associated membrane protein-2 because of mutations in the lysosome-associated membrane protein-2 gene. Classic clinical features in males include cardiomyopathy (100%, eventually), myopathy (90%), and mental retardation (70%), but mostly of a mild degree. We report on an unusual presentation in a patient with autism, motor delay, and a normal cardiac evaluation. The presence of multiorgan involvement, including elevated liver enzymes, abnormal cranial magnetic resonance imaging, and diffuse hypotonia with swallowing difficulties, prompted a muscle biopsy. A quadriceps muscle biopsy was performed, and the findings were most suspicious for a glycogen storage-type disease. Subsequently, a pathogenic lysosome-associated membrane protein-2 mutation was found. To our knowledge, there are no previous clinical reports of autism in children with Danon disease.