RESUMO
Floppy infant syndrome (FIS) refers to a condition wherein an infant manifests generalized hypotonia since birth or in early life. It is heterogeneous and can be caused by various central nervous system disorders, neuromuscular diseases and genetic disorders. X-linked myotubular myopathy (XMTM) is a progressive congenital myopathy morphologically characterized by the presence of centrally placed nuclei in numerous muscle fibers without any other particular pathological abnormalities. Patients are frequently born with floppiness and respiratory distress. The vast majority of patients carry a truncating or missense mutation in MTM1. The authors report here a full term male baby with clinicopathological features of XMTM. The diagnosis is validated by the finding of a c. 141-144delAGAA mutation ofMTM1. To the best of the authors' knowledge, the present case is the first genetically confirmed XMTM in Thailand. A brief review of various neuromuscular disorders causing floppy infant syndrome is also included.
Assuntos
Cromossomos Humanos X , Doenças Genéticas Ligadas ao Cromossomo X/genética , Miopatias Congênitas Estruturais/genética , Proteínas Tirosina Fosfatases/genética , Mapeamento Cromossômico , Análise Mutacional de DNA , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/etnologia , Humanos , Recém-Nascido , Masculino , Miopatias Congênitas Estruturais/diagnóstico , Miopatias Congênitas Estruturais/patologia , Linhagem , Proteínas Tirosina Fosfatases não Receptoras , TailândiaRESUMO
The authors share experiences in taking care of 27 cases of childhood onset myasthenia gravis (MGS). In all cases, the diagnosis was confirmed by a combination of clinical examination and Neostigmine test. The majority (92%) had localized ocular myasthenia with median onset of symptoms at 33 months of age. About 24 per cent of them progressed to generalized MGS. A few (8%) presented with respiratory failure that required ventilatory support with onset of symptoms at about 22 months. Thymectomy was performed in 10 cases. Complete and partial remissions were achieved in about 70 per cent and 26 per cent of cases respectively with the combination of an immunosuppressant (azathioprine) and a Cholinesterase inhibitor (pyridostigmine). None experienced a myasthenic crisis with proper management and good follow-up using the above combinations.
Assuntos
Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiologia , Adolescente , Distribuição por Idade , Idade de Início , Azatioprina/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Incidência , Masculino , Miastenia Gravis/tratamento farmacológico , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Esteroides/administração & dosagem , Tailândia/epidemiologia , Timectomia/métodos , Resultado do TratamentoRESUMO
Dysferlinopathy refers to a variety of autosomal recessive, skeletal muscle disorders due to the mutations of dysferlin-encoding gene, DYSF. It encompasses limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), distal myopathy with anterior tibial onset (DMAT), isolated hyperCKemia, rigid spine syndrome and congenital muscular dystrophy. Herein, we report five Thai patients with distal myopathy due to dysferlinopathy including four MM and one DMAT patients. Muscle biopsy from one MM patient depicted numerous ring fibers which is an atypical finding in dysferlinopathy. Mutation analysis of DYSF revealed novel compound heterozygous mutations of p.Tyr309X and c.236+1G>T in two related MM patients, known homozygous mutations, p.Arg89X and p.Gln176X, in two MM patients and a heterozygous missense mutation, p.Arg555Trp, in a DMAT patient. Most of the previously reported DMAT patients were Hispanic. To the best of our knowledge, this is the first report of genetically confirmed patients with dysferlinopathy in Thailand.
Assuntos
Miopatias Distais/genética , Proteínas de Membrana/genética , Proteínas Musculares/genética , Adulto , Western Blotting , Creatina Quinase/sangue , Miopatias Distais/epidemiologia , Miopatias Distais/patologia , Disferlina , Éxons/genética , Família , Feminino , Humanos , Imuno-Histoquímica , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Força Muscular , Músculo Esquelético/patologia , Mutação/fisiologia , Polimorfismo Genético/genética , Polimorfismo Genético/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tailândia/epidemiologia , Adulto JovemRESUMO
Distal myopathy with rimmed vacuoles (DMRV) is an early-adult-onset, distal myopathy caused by a mutation of the UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE) gene. We herein report four Thai patients with DMRV who carried compound heterozygous mutations of the GNE gene including three novel (p.G89R, p.P511T, and p.I656N) and two known mutations (p.A524V and p.V696M). All patients shared p.V696M in one allele. Our study demonstrates the mutation spectrum of the GNE gene in Thai patients with DMRV.