Miopatía nemalínica tratada con L-tirosina para aliviar los síntomas en un recién nacido / Nemaline rod myopathy treated with L-tyrosine to relieve symptoms in a neonate

La miopatía nemalínica es un trastorno heterogéneo definido por la presencia de estructuras con forma de bastones, conocidas como cuerpos nemalínicos (o bastones de nemalina). El diagnóstico se funda en la debilidad muscular, además de la visualización de cuerpos nemalínicos en la biopsia muscular. La miopatía nemalínica no tiene cura. Las estrategias terapéuticas para este trastorno son sintomáticas y empíricas. En este artículo, presentamos el caso de una recién nacida con insuficiencia respiratoria grave y debilidad muscular generalizada, a la que se le diagnosticó miopatía nemalínica a través de la biopsia muscular. La paciente tuvo una notable disminución de la sialorrea y una mejora de los movimientos espontáneos después del tratamiento con L-tirosina. Este caso se presenta para destacar la importancia de la biopsia muscular en el diagnóstico diferencial de la hipotonía grave durante el período neonatal y el posible beneficio del aporte suplementario de L-tirosina para disminuir la sialorrea y restaurar la fuerza muscular.

Nemaline myopathy (NM) is a heterogeneous disorder defined by the presence of rod-shaped structures known as nemaline bodies or rods. The diagnosis is based on muscle weakness, combined with visualization of nemaline bodies on muscle biopsy. There is no curative treatment for nemaline myopathy. Therapeutic strategies for this condition are symptomatic and empirical. Herein, we present a newborn with severe respiratory failure and generalized muscle weakness, who was diagnosed as NM by muscle biopsy. The patient experienced remarkable decrease in sialorrhea and improvement of spontaneous movements after L-tyrosine treatment. This case is presented to emphasize the importance of muscle biopsy in the differential diagnosis of severe hypotonia during neonatal period and a possible benefit of L-tyrosine supplementation for decreasing sialorrhea and restoring muscle strength.

A Family of Congenital Fiber Type Disproportion with Mutation in Tropomyosin 3 (TPM3) Gene Presenting as Altered Mentality with Respiratory Distress

Congenital fiber type disproportion (CFTD) has been related with mutations in ACTA1, SEPN1, RYR1 and tropomyosin 3 (TPM3) genes. Particularly, TPM3 mutation was identified as one of the most frequent cause of CFTD and was also detected in cap myopathy and nemaline myopathy. Herein we report patients of autosomal dominant TPM3 missense mutations with CFTD in a Korean family over twogenerations. Two of our patients, who developed mild muscle weakness in infancy, presented with altered mentality and respiratory distress despite relatively mild limb weakness.

A Mutation in the ACTA1 gene Manifesting Nemaline Myopathy with Central Nervous System Lesions

No abstract available.

Nemaline Myopathy Presenting as Adult-onset Distal Myopathy / 대한임상신경생리학회지

No abstract available.

Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

Little is known regarding cardiac involvement (CI) by neuromuscular disorders (NMDs). The purpose of this review is to summarise and discuss the major findings concerning the types, frequency, and severity of cardiac disorders in NMDs as well as their diagnosis, treatment, and overall outcome. CI in NMDs is characterized by pathologic involvement of the myocardium or cardiac conduction system. Less commonly, additional critical anatomic structures, such as the valves, coronary arteries, endocardium, pericardium, and even the aortic root may be involved. Involvement of the myocardium manifests most frequently as hypertrophic or dilated cardiomyopathy and less frequently as restrictive cardiomyopathy, non-compaction, arrhythmogenic right-ventricular dysplasia, or Takotsubo-syndrome. Cardiac conduction defects and supraventricular and ventricular arrhythmias are common cardiac manifestations of NMDs. Arrhythmias may evolve into life-threatening ventricular tachycardias, asystole, or even sudden cardiac death. CI is common and carries great prognostic significance on the outcome of dystrophinopathies, laminopathies, desminopathies, nemaline myopathy, myotonias, metabolic myopathies, Danon disease, and Barth-syndrome. The diagnosis and treatment of CI in NMDs follows established guidelines for the management of cardiac disease, but cardiotoxic medications should be avoided. CI in NMDs is relatively common and requires complete work-up following the establishment of a neurological diagnosis. Appropriate cardiac treatment significantly improves the overall long-term outcome of NMDs.

Prevalencia de alteraciones de la creatina-fosfoquinasa (CPK) sérica en pacientes que toman estatinas / Prevalence of abnormalities of creatine phosphokinase (CPK) levels in patients taking statins

El uso de estatinas para combatir la dislipidemia se asocia con un espectro de síntomas musculares que van desde mialgias con o sin aumento de la creatina-fosfoquinasa (CPK), hasta rabdomiólisis fatal. Objetivo: determinar la prevalencia de la elevación de la CPK en pacientes que toman estatinas y determinar los posibles factores de riesgo asociados al aumento de la CPK en estos pacientes. Métodos: estudio observacional de corte transversal en el que se evaluaron las alteraciones de la CPK en una población de 503 pacientes con tratamiento con estatinas para el control de la dislipidemia, y que asisten al Laboratorio Clínico Hematológico en Medellín, Colombia por razones diferentes a la medición de la CPK. Mediante un cuestionario aplicado a los pacientes se obtuvieron los datos demográficos, los antecedentes personales y el tipo de estatina utilizada. Resultados: 56 (11,1 por ciento) pacientes presentaron aumento de la CPK por encima del rango de referencia normal; 7 pacientes (1,4 por ciento) tenían un aumento dos veces por encima del valor superior normal, y de ellos 3 (0,6 por ciento) tenían un aumento tres veces por encima del valor superior normal. Se encontró asociación significativa entre niveles altos de la CPK con el sexo masculino y con el uso de inhibidores selectivos de la recaptación de serotonina (ISRS). No se encontró asociación con otros factores de riesgo previamente descritos en otros estudios como son el ejercicio, el consumo de alcohol, el hipotiroidismo y la dosis de estatinas, entre otros. En cuanto a síntomas musculares, el 28,4 por ciento relató dolor muscular con el uso de estatinas, 26 por ciento cansancio y 15,9 por ciento debilidad muscular. Conclusión: los hallazgos de este estudio demuestran que el aumento asintomático de la CPK en pacientes que toman estatinas para la reducción por ciento del colesterol, es mayor al previamente reportado y confirma que el sexo masculino y el uso de fármacos tipo ISRS se relacionan con un aumento de la CPK. También se encontró que el porcentaje de pacientes con síntomas musculares, especialmente dolor y cansancio, es mucho mayor a lo reportado en la literatura mundial. Desde el punto de vista clínico se desconocen las repercusiones que pueda tener el aumento asintomático de la CPK, lo que requeriría estudios de seguimiento a largo plazo.

Clinical Heterogeneity in Korean Patients with Nemaline Myopathy

PURPOSE: Nemaline myopathy (NM) is a clinical heterogeneous congenital myopathy characterized by the presence of subsarcolemmal or cytoplasmic rod-like structures that call nemaline bodies in the muscle fibers. The purpose of this study was to investigate the clinical diversity and pathological features of Korean patients with NM. MATERIALS AND METHODS: Eight patients underwent analyses of clinical manifestations by a structured protocol. Diagnoses were established by a muscle biopsy. RESULTS: Two patients had the typical congenital type, which exhibited neonatal hypotonia and delayed motor milestone, and five patients had the childhood onset type, which exhibited mild gait disturbance as a first symptom. One patient had the adult onset type, which showed acute respiratory failure. Limb weakness was proximal-dominant occurred in six patients. Hyporeflexia was observed in most patients. Elongated faces and high arched palates and feet were also observed. On light microscopy, the nemaline bodies were observed in type 1 and 2 fibers. All patients showed type 1 predominance and atrophy. In the two cases in which ultrastructural studies were performed, typical nemaline rods and disorganized myofibrillar apparatus were detected. CONCLUSION: In conclusion, the eight Korean patients in this study with NM shared common clinical expressions such as proximal limb weakness, reduced deep tendon reflex, and dysmorphic features. This study, however, showed that clinical heterogeneity ranged from typical congenital, mildly affected childhood to the adult onset form with acute respiratory failure. The pathological findings in this study were in accordance with those of other previous reports.

Nemaline myopathy: clinical, histochemical and immunohistochemical features / Miopatia nemalínica: achados clínicos, histoquímicos e imuno-histoquímicos

Nemaline myopathy (NM) is a congenital disease that leads to hypotonia and feeding difficulties in neonates. Some cases have a more benign course, with skeletal abnormalities later in life. We analyzed a series of eight patients with NM obtained from a retrospective analysis of 4300 muscle biopsies. Patients were classified as having the typical form in five cases, intermediate form in two cases and severe form in one case. Histochemical analysis showed mixed rods distribution in all cases and predominance of type I fibers in five cases. Immunohistochemical analysis showed abnormal nebulin expression in all patients (four heterogeneous and four absent), homogeneous desmin expression in four cases, strongly positive in three and absent in one, fast myosin expression in a mosaic pattern in six cases and absent in two cases. There was no specific relation between these protein expression patterns and the clinical forms of NM.

Miopatia nemalínica (NM) é uma doença congênita que leva a hipotonia e dificuldade de sugar em neonatos. Alguns casos possuem uma evolução benigna, com deformidades ósseas tardias. Nós analisamos uma série de oito pacientes com NM obtidos da análise retrospectiva de 4300 biópsias musculares. Os pacientes foram classificados como forma típica em cinco casos, forma intermediária em dois casos e forma severa em um caso. Análise histoquímica mostrou distribuição mista dos rods em todos os casos e predominância de fibras tipo I em cinco casos. Análise imuno-histoquímica mostrou expressão anormal da nebulina em todos os pacientes (quatro heterogênea e quatro ausente), expressão homogenea da desmina em quatro casos, fortemente positiva em tres e ausente em um, expressão da miosina (rápida) com padrão em mosaico em seis casos e ausente em dois casos. Não há relação específica entre a expressão destas proteínas e as formas clínicas da NM.

Congenital myopathies: a clinicopathological study of 25 cases.

OBJECTIVE: Congenital myopathies are rare. Through this article, the authors want to present a clinicopathological analysis of 25 new cases. MATERIALS AND METHODS: The clinical data of patients who were diagnosed with congenital myopathy between 2001 and 2006 was retrieved. Muscle biopsies were processed for H&E staining, enzyme histochemistry, and immunohistochemistry. Biopsies were also processed for ultrastructural analysis. RESULTS: During a period of 6 years, 1.12% of the muscle biopsies were diagnosed as congenital myopathies. The most common congenital myopathy was central core disease followed by nemaline rod myopathy and multi-mini core disease. Clinically, they have variable features. The final diagnosis was made with the help of enzyme histochemistry and ultrastructural features. CONCLUSION: This study emphasizes the importance of enzyme histochemistry and electron microscopic examination in the diagnosis of congenital myopathies especially in the absence of genetic studies.

Nemaline rod myopathy: a rare form of myopathy.

Nemaline rod myopathy (NM) is a rare form of congenital myopathy characterized by slowly progressive or nonprogressive muscle weakness and pathognomonic rod-like structures within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. All cases of NM diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. During a period of 1.5 years (Jan 2004 to June 2005), we received 750 muscle biopsies for various reasons. Of which, 15 were diagnosed as congenital myopathies and four as nemaline rod myopathies. Thus, NM comprises 0.53% of all muscle diseases and 22.6% of all congenital myopathies. All of them presented in childhood (first five years of life) with generalized hypotonia, feeding problems, repeated respiratory infections and muscle weakness. Both males and females were equally affected. The CPK levels were normal and EMG was myopathic. Microscopic examination revealed minimal changes but characteristic red-colored material was seen on modified Gomori trichrome staining which was immunopositive to alpha actinin. Ultrastructural examination confirmed this material to be nemaline rods. NM, although a rare form of congenital myopathies, should be suspected in children who present with generalized hypotonia, repeated chest infections and slowly progressive muscle weakness. This report highlights the importance of histochemistry and ultrastructural examination in the diagnosis of this entity, in the absence of the availability of methodology for genetic studies.

Atrofia muscular neurogénica en miopatía nemalínica: ¿fenómeno primario o secundario? a propósito de un caso / Neurogenic muscular atrophy in nemaline myopathy: ¿primary or secondary phenomenon? case report

La miopatía nemalínica es una miopatía congénita estructural que cursa con debilidad muscular generalmente no progresiva y se caracteriza por la presencia de los llamados "bastones" o "nemalines" en las fibras musculares. Se presenta el estudio anatomoclínico de una forma neonatal severa de la enfermedad en la cual encontramos, además, atrofia muscular neurogénica y escasas motoneuronas de la médula espinal con degeneración simple, sin otra evidencia de denervación. Se revisan otros casos similares descritos en la literatura y se plantea la posibilidad de un trastorno de la inervación, o bien, que el daño muscular por nemalines ocasione una lesión neurogénica por vía retrógrada

Miopatia nemalínica: relato de caso clínico / Nemaline myopathy: case report

O presente trabalho descreve o caso clínico de uma criança do sexo feminino portadora de miopatia nemalínica, também conhecida como miopatia em bastões. Esta patologia é uma forma rara de miopatia congênita, de natureza progressiva, caracterizada por fraqueza muscular de início na infância e pela presença de estruturas em forma de bastão dentro das fibras musculares. A fraqueza muscular é geralmente mais severa na face, nos músculos flexores do pescoço e dos membros. Ao nascimento pode manifestar-se por poucos movimentos espontâneos, além de dificuldades alimentares, caracterizadas por deglutição e sucção fracas, complicadas por refluxo gastroesofágico; estas podem levar à desnutrição e concorrer para infecções respiratórias recidivantes e insuficiência respiratória. O grau de fraqueza muscular determinará o comprometimento na fala, no vedamento labial, na respiração e conseqüentemente nas alterações oclusal e da articulação temporomandibular. O objetivo deste trabalho é esclarecer e auxiliar os cirurgiões-dentistas e odontopediatras na identificação das características gerais e bucais desta patologia para que o diagnóstico precoce, reabilitação e acompanhamento multidisciplinar sejam estabelecidos desde a constatação da miopatia nemalínica, melhorando o estado de saúde do paciente

A Case of Nemaline Myopathy

Childhood onset nemaline myopathy, first described in 1963 by Shy, et al and Conen, et al, is rare congenital myopathy, characterized by nonprogressive or slowly progressive muscle weakness associated with rod-like structures in muscle fibers, often with dysmorphic features. This myopathy was confirmed by muscle biopsy. The light microscopic features noted generally small round fibers that showed variation in size and occasional internal nuclei and characteristic rod bodies that could be demonstrated in the longitudinal sections stained with modified Gomori trichrome stain. Electromicroscopically there were accumulations of numerous irregular electron dense materials scattered between the myofibrils, particularly under the sarcolemma and enlargement and streamimg of the Z disk. We report a case of childhood onset nemaline myopathy in Korea in a 7 year- old boy who had nonprogressive muscle weakness of the limbs with a waddling gait.

A Case of Adult Onset Nemaline Myopathy with Selective Respiratory Muscle Weakness

Nemaline myopathies, originally reported as a type of congenital myopathy, are clinically and genetically heterogenous diseases. Clinically, nemalin myopathies can be divided into infantile, juvenile and adult forms, and genetically, into autosomal dominant and recessive. There are several reports on nemalin myopathy in Korea, all juvenile forms, but not adult or infant form. In contrast to juvenile form, the adult congential nemalin myopathy is characterized by rather selective acute or subacute respiratory dysfunction in adult age with sporadic or autosomal recessive inheritance. Here, we report the first case of an adult form of nemalin myopathy, whose symptoms were rapidly developed at the age of 32. Therefore, nemalin myopathy can be included in the differential diagnosis for the unexplainable respiratory failure in adult age.

Anesthetic Experience of the Patient with Nemaline Myopathy: A case report / 대한마취과학회지

Nemaline rod myopathy is an autosomal dominant disease characterized by nonprogressive symmetric skeletal muscle weakness affecting principally proximal skeletal muscles. Anesthesia of the patient with this disease is known to present some problems:difficult intubation due to facial dysmorphism, delayed onset of succinilcholine, reduced vital capacity on pulmonary function test and skeletal deformity. We anesthetized 19 year old male patient with nemaline myopathy for the operation of cryptochidism. Because of the possibility of difficult intubation, we produced epidural anesthesia with 20 G Tuohy needle at L5-S1 intervertebral space successfully. There were no problems in the course of operation and recovery except transient airway obstruction due to sedative.

Miopatía nemalínica: primer caso nacional reportado / Nemaline myopathy: first case reported in the country

El desarrollo de las técnicas para el estudio histopatológico de la biopsia muscular ha permitido por primera vez en el país diagnosticar una miopatía nemalínica en una niña de 2 años y 10 meses de edad, portadora de una afección muscular presente en los primeros meses de vida y complicada por tres episodios de tipo respiratorio. El diagnóstico fue realizado ante la presencia de abundantes cuerpos nemalínicos en importante proporción de las fibras musculares y en ausencia de otras alteraciones estructurales. La presentación clínica de todas las miopatías es similar, destacándose el valor del estudio histopatológico por un equipo especializado como único procedimiento para definir el diagnóstico

Miopatia nemalínica com corpos intracitoplasmáticos esferóides: relato de caso / Nemalinic myopathy with intracytoplasmic spheroid bodies: a case report

Os autores relatam o caso de paciente do sexo feminino de 18 anos de idade com fraqueza lentamente progressiva nos quatro membros desde a infância, sem antecedentes relevantes. O exame neurológico mostrou déficit motor discreto proximal e distal com retraçao muscular leve ao nível de ombros, cotovelos, articulaçoes coxo-femurais, joelhos e tornozelos; hipotrofia muscular nas pernas e pés: reflexos presentes e sensibilidade normal. Creatinofosfoquinase com aumento de uma vez e meia o valor normal. Eletroneuromiografia: diminuiçao de amplitude e duraçao dos potenciais de açao e traçado de interferência paradoxal, compatíveis com afecçao muscular primária. Biópsia muscular em congelaçao (HE, Gomori, PAS, ATPases, NADH, SDH, fosfatases ácida e alcalina, citocromo-c-oxidase e Oil-red-O) revelou afecçao muscular primária caracterizada pela presença de corpos nemalínicos e corpos intracitoplasmáticos esferóides. Os corpos nemalínicos podem ser encontrados com diferentes alteraçoes das fibras musculares, porém essa associaçao é rara. Este é o segundo relato da associaçao entre corpos nemalínicos e esferóides.

A Familial Nemaline Myopathy

Nemaline myopathy is a rare congenital m opathy, characterized by nonprogressive or slowely progressive muscle weakness associated with rod-like structures in muscle fibers and characteristic dysmorphic features. We report the first farnilial nemaline myopathy in two generations of the same family, confirmed by muscle biospy in an 11-year-old boy and his mother. The patients had hypotonia and slowly progressive muscle weakness of the four limbs associated with characteristic facial dysmorphism and skeletal deformities. Light and electron microscopic study of a muscle biopsy showed numerous nemaline rods in both patients.

Electromyographic & clinical features of nemaline myopathy

No abstract available.