Altered myogenesis and premature senescence underlie human TRIM32-related myopathy.

TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knock-in mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation.

Non-compaction cardiomyopathy and early respiratory failure in an adult symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation.

X-linked myotubular myopathy (XLMTM) is a rare neuromuscular condition caused by mutations in the MTM1 gene. Female carriers are believed to be usually asymptomatic; nevertheless, recent reports have displayed a wide a spectrum of clinical involvement in females suggesting that MTM1 mutations might be underestimated in this population. Here we report a 55-year-old woman manifesting with an abrupt respiratory decline, whose respiratory function tests revealed a severe restrictive ventilatory defect. The neurological examination identified mild proximal leg weakness and her cardiac evaluation showed a non-compaction cardiomyopathy with normal left ventricle function. Muscle biopsy was consistent with centronuclear myopathy. Next-generation sequencing of 49 genes related to congenital myopathies allowed the identification of a 4 bp deletion in the MTM1 gene, leading to a truncating mutation previously described in males but for the first time reported in a female patient.

[Reversible alterations in the neuroimages associated with vigabatrine treatment in infants with epileptic spasms]. / Alteraciones reversibles en la neuroimagen asociadas al tratamiento con vigabatrina en lactantes con espasmos epilepticos.

INTRODUCTION: Vigabatrin (VGB) is a first-line drug for the treatment of infantile spasms. Recently, several reports claim the existence of abnormalities in magnetic resonance imaging (MRI) (particularly affecting basal ganglia, and visible in T2 and diffusion sequences) in infants with spasms that were receiving high doses of VGB (> 100 mg/kg/day), which appear to be reversible after withdrawal of treatment. CASE REPORTS: We present two cases with an epileptic encephalopathy in the first year of life and seizures consisting of infantile spasms. Both were treated with several antiepileptic drugs, including VGB up to a maximum dosage of 200 mg/kg/day. At the age of 11 and 28 months, respectively, MRI images showed marked signal hyperintensities on T2-sequences on bilateral globus pallidus, thalamus, posterior portion of the brainstem and dentate nuclei, also visible on diffusion sequences. Both had previous unaltered MRI studies. After excluding an underlying metabolic disease, VGB withdrawal is decided, appreciating the reversibility of those lesions in a prospective MRI study, three months later. CONCLUSIONS: We must consider and carefully evaluate findings on brain MRI in infants receiving VGB at high doses for treatment of spasms. The apparent cytotoxic effect on basal ganglia could simulate metabolic/mitochondrial diseases. By knowing this effect of VGB and its typical MRI features, unnecessary testing can be avoided in young infants with epileptic encephalopathies, including complex procedures like muscle biopsy or a new metabolic screening.

TITLE: Alteraciones reversibles en la neuroimagen asociadas al tratamiento con vigabatrina en lactantes con espasmos epilepticos.Introduccion. La vigabatrina (VGB) es un farmaco de primera linea para el tratamiento de espasmos infantiles. Diversos estudios han hallado anomalias en la resonancia magnetica (RM) cerebral, que afectaban particularmente a los ganglios de la base, y especialmente en secuencias de difusion, en lactantes con espasmos que recibian VGB en altas dosis (> 100 mg/kg/dia), y se ha observado la desaparicion de las lesiones tras la retirada de dicho tratamiento. Casos clinicos. Se presentan dos casos clinicos con inicio de una encefalopatia epileptica en el primer año de vida y crisis en forma de espasmos infantiles. Ambos recibieron tratamiento con distintos farmacos, entre ellos VGB hasta dosis de 200 mg/kg/dia. Con 11 y 28 meses de vida, respectivamente, aparecian imagenes en la RM cerebral con una marcada hiperintensidad de señal en secuencias ponderadas en T2 en ambos palidos, talamos, porcion posterior del tronco encefalico y nucleos dentados, que asociaban restriccion en secuencias de difusion. Ambos disponian de estudios previos de RM, sin alteraciones. Tras excluir una metabolopatia subyacente, se decidio la retirada de la VGB y tres meses despues, en una RM de control, se aprecio la total reversibilidad de dichas lesiones. Conclusiones. Deben evaluarse con cautela los hallazgos de la RM cerebral en lactantes que reciban VGB en altas dosis para el tratamiento de espasmos. Su aparente efecto citotoxico sobre los ganglios de la base podria simular metabolopatias/enfermedades mitocondriales. Conocer este efecto de la VGB y sus caracteristicas tipicas en la RM puede evitar pruebas innecesarias, como una biopsia muscular o un nuevo cribado metabolico.

Protocolo de Fisioterapia en el paciente parkinsoniano / Protocol for physical therapy in parkinsonism patient

La enfermedad de Parkinson se presenta como un cuadro muy frecuente entre la población perteneciente a la tercera edad, de modo que afecta al 1 por ciento de los mayores de 65 años y al 2 por ciento de los sujetos de 85 años o más. Se calcula que en España hay unos 70.000 enfermos, con una incidencia estimada de 16/100.000 personas y una prevalencia de 1.000/100.000 personas. En este artículo de revisión presentamos una propuesta de protocolo de Fisioterapia para individuos afectados de la enfermedad de Parkinson. Este protocolo ha sido desarrollado en base a una revisión bibliográfica y a la experiencia acumulada a lo largo de cinco años en dos centros geriátricos: la Residencia Asistida de la Tercera Edad de Oleiros y la Residencia de la Tercera Edad Torrente Ballester en A Coruña. Asimismo se propone una clasificación evolutiva propia de Fisioterapia para el enfermo de Parkinson. Comenzamos el artículo con una introducción, mostrando la fisiopatología y la clínica de la enfermedad, que posteriormente relacionamos entre sí y con los objetivos de Fisioterapia, para más adelante presentar el tratamiento fisioterápico utilizado para cumplimentar cada uno de los objetivos propuestos (AU)

[Prevalence of cardiovascular risk factors in a working population]. / Prevalencia de factores de riesgo cardiovascular en población laboral.

BACKGROUND: A high prevalence of cardiovascular risk factors (RF) has been reported in Spain. The aim of this study was to determine the main RF of heart disease (cholesterol, smoking, high blood pressure (HBP), diabetes, obesity, and sedentarism) in laboral population from Granada, Spain. METHODS: The sample included 1,555 workers (1,193 males and 362 females, mean age 42.3 years). The percentage of participation was 91.9%. Information was collected directly (standardized self administered questionnaire) and from the physicians of the companies (protocolized anamnesis, physical examination and electrocardiogram) for each worker. Serum cholesterol was measured in venous blood by an enzymatic autoanalyzer. A description of the phenomennon was studied and likewise, the multivariate models of logistic regression were adjusted to evaluate the association of the other RF with hypercholesterolemia. RESULTS: Serum cholesterol level higher than 200 mg/dl (5.17 mmol/l) was presented in 69.3% of the sample. The prevalence of HBP was 8.4%. Forty-four point two percent were smokers (48.9% males and 28.7% females). A body mass index higher than 25 kg/m2 was presented in 65.2%. The prevalence of diabetes was 3.5% and 18% of the workers classified themselves as sedentary. Only 2.8% of the males and 11.6% of the females were absolutely free of the RF studied. Diabetes, age, obesity, HBP and smoking (> 10 cigarettes/day) were significantly associated with a higher probability to present hypercholesterolemia. CONCLUSIONS: A high prevalence of classical risk factors related to cardiovascular disease, with the exception of high blood pressure, was observed, thus making the application of preventive measures necessary.

Evidence for the safety of coumaphos, diazinon and malathion residues in honey.

Residue levels of coumaphos, diazinon and malathion in honey were analysed in 177 samples of honey collected from different regions of Lugo in NW Spain in 1988-1990. One has to expect some of them as residues in honey, even if employed properly, for example coumaphos used against the parasitic mite Varroa jacobsoni. Honey samples were extracted with acetonitrile:water (2:1 v/v), partitioned with petroleum-ether, cleaned up with a manual Florisil column or Florisil Sep-Pack, evaporated to dryness, redissolved in an appropriate volume (1 mL) and then analyzed by GLC with a silica capillary column and nitrogen-phosphorus detector. Recoveries of coumaphos, diazinon and malathion varied between 80-97%. One hundred forty-eight samples contained no detectable residues, while 29 had residues of coumaphos and diazinon in ppb levels. These residues are minimal and when eating honey are harmless for the health of human beings.