Familial amyloidosis with polyneuropathy type 1 caused by transthyretin mutation Val50Met (Val30Met): 4 cases in a non-endemic area

Introduction: Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) typically arises as an autonomic neuropathy primarily affecting small fibres and it occurs in adult patients in their second or third decades of life. It progresses rapidly and can lead to death in approximately 10 years. Other phenotypes have been described in non-endemic areas. Objectives and methods: We described 4 cases from the Spanish province of Guipuzcoa, a non-endemic area, to highlight the clinical variability of this disease. Patients and results: Three patients presented a late-onset form manifesting after the age of 50, featuring a predominantly motor polyneuropathy initially causing distal impairment of the lower limbs followed by the upper limbs. One patient suffered severe neuropathic pain. None showed signs of autonomic involvement. The fourth patient, of Portuguese descent, presented a typical form with onset in her thirties, neuropathic pain and dysautonomia. All patients carry the Val50Met mutation in the TTR gene. Conclusion: FAP is a pleomorphic disease even in patients carrying the same mutation. In non-endemic areas, its main form of presentation may resemble a predominantly motor polyneuropathy developing in the sixth decade of life with no signs of dysautonomia. Given this non-specific presentation and the widely available technical means of studying the TTR gene, we believe that the protocol for the aetiological diagnosis of any polyneuropathy should include genetic sequencing of TTR. (C) 2016 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U

Trimetazidine Induces Parkinsonism, Gait Disorders and Tremor

Objective: To study the adverse effects of trimetazidine on motor functions. Design: A retrospective study was carried out using electronic records to identify all patients seen between January 1990 and August 2003. Setting: A neurological out-patient clinic. Participants: Of the 10 258 patients who attended the clinic, 130 received trimetazidine. Treatment with this drug was discontinued in 128 patients. Of the 130 patients treated with trimetazidine, 29 also had other drugs capable of inducing parkinsonism withdrawn from their treatment. Main outcome measures: Identification of an improvement in motor function after drug withdrawal. Results: In 56 of the 130 patients who were treated with trimetazidine (43%), an adverse effect on motor function was detected that had been induced or aggravated by one of the withdrawn drugs. Indeed, druginduced parkinsonism was detected in 20 of these patients. Of these, ten were being treated with trimetazidine only, while the remaining ten were simultaneously receiving other drugs potentially capable of inducing parkinsonism. Treatment with trimetazidine worsened previously diagnosed Parkinson's disease in 12 patients, and gait disorders coupled with disequilibrium was observed in 15 patients. Trimetazidine induced tremor in nine patients. Conclusion: Trimetazidine can induce parkinsonism, gait disorder and tremor. These adverse effects have not been previously described for this drug

The Discovery of the Dardarin Gene 15 Years Later: A Globalized Local History

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Gerri distrofia muskularra Gipuzkoan

Gracias a los avances producidos en la genética molecular, el concepto de Distro a Muscular Lumbar (LGMD) está cambiando rápidamente. Se han descrito diferentes loci y ha quedado probado que el síndrome de Distro a muscular Lumbar es heterogéneo. Hemos realizado un examen epidemiológico en Gipuzkoa y hemos encontrado la prevalencia mayor de LGMD descrita hasta la fecha: 69/106. La mutación en el gen Kalpaina3 que evidencian los afectados muestra características clínicas similares que son distintas a las características de otros grupos, lo cual posibilita un diagnóstico clínico preciso.Genetika molekularrean egindako aurrerapausoeri esker, Gerri Distro a muskularren (LGMD) kontzeptua azkar ari da aldatzen. Loci desberdinak deskribatu dira Gerri Distro muskularra sindrome heterogeneoa dela frogatuz. Azterketa epidemiologikoa burutu dugu Gipuzkoan eta gaurdaino deskribaturiko LGMD-en prebalentzirik altuena aurkitu dugu: 69/106. Kalpaina3 genean mutazioa duten gaisoek, antzeko ezaugarri klinikoak agertzen dituzte beste taldeen ezaugarriekiko desberdinak direlarik, horrela diagnostiko kliniko zehatza baimenduz.Grâce aux progrès qui ont été fait dans le domaine de la génétique moléculaire, le concept de Dystrophie Musculaire Lombaire (LGMC) est en train de changer rapidement. On a décrit différents loci et il a été prouvé que le syndrome de Dystrophie musculaire Lombaire est hétérogène. Nous avons réalisé un examen épidémiologique en Gipuzkoa et nous avons trouvé la plus importante prévalence de LGMD décrite jusqu'à cette date: 69/106. La mutation dans le gène Kalpaina3 que les personnes affectées mettent en évidence montre des caractéristiques cliniques similaires qui sont différentes des caractéristiques d'autres groupes, ce qui permet un diagnostique clinique précis.Thanks to the advances that have taken place in molecular genetics, the concept of Limb-Girdle Muscular Dystrophy (LGMD) is rapidly changing. Various loci have been described and it has been proved that the Limb-Girdle Muscular Dystrophy syndrome is heterogeneous. We have carried out an epidemiological examination in Gipuzkoa and we have found the highest LGMD prevalence described up to the present: 69/106. The mutation in gen Kalpaina3 displayed by those affected shows similar clinical characteristics to those of other groups, which makes a precise clinical diagnosis possible

Mutazioak progranulina genean: eragiten duten klinika, patologia eta RNA mailako adierazpena

La degeneración del lóbulo frontotemporal (FTLD) es un complejo grupo de enfermedades que se clasifican dentro de las demencias. En este trabajo presentamos los análisis clínicos, moleculares y patológicos de una serie de enfermos que padecen FTLD. Entre los 72 enfermos hemos encontrado 4 mutaciones diferentes y 14 enfermos portadores de mutación. Además, hemos medido el nivelde expresión del gen PGRN que se encuentra en las células de la sangre y demostramos que se puede utilizar como marcador biológico de la enfermedad.Garuneko lobulu fronto-tenporalaren degenerazioa (FTLD) dementzien barruan sailkatzen den gaixotasun talde konplexu bat da. Lan honetan FTLD duten gaixo serie baten analisi kliniko, molekular eta patologikoak aurkezten ditugu. 72 gaixoen artean 4 mutazio desberdin aurkitu ditugu eta 14 mutaziodun gaixo. Gainera, odoleko zeluletan aurkitzen den PGRN genearen adierazpen maila neurtudugu eta gaixotasunaren markatzaile biologiko bezela erabil litekela erakusten dugu.La dégénération du lobe fronto-temporel (FTLD) fait partie d'un complexe groupe de maladies qualifiées de démences. Ce travail présente les résultats des prélèvements cliniques, moléculaires et pathologiques effectués chez toute une série de malades atteints de FTLD. Parmi les 72 malades analysés, nous avons trouvé 4 mutations différentes et 14 malades porteurs de mutatión. Nous avons, par ailleurs, mesuré le niveau de expression du gène PGRN qui se trouve dans les cellules du sang, pour démontrer qu'il peut être utilisé comme marqueur biologique de la maladie.The degeneration of the frontotemporal lobe (FTLD) is a complex group ofillnesses which are classified within those of dementia. In this work we present the clinical analysis, molecular and pathologic, of a series of patients who suffer from FLD. Among the 72 patients we found 4 different mutations and 14 mutated patients. In addition we have measured the level of representation of the PGRN gene which is found in the blood cells and we have demonstrated that it can be used as a biological indicator of the illness

Epilepsia eta Genetika

El aislamiento de determinados genes que intervienen en el origen de la epilepsia idiopática ha permitido una mejor clasi cación de la epilepsia. En el presente trabajo se da cuenta del examen clínico de dos familias con síndrome epiléptico. La primera muestra una epilepsia nocturna asociada al cromosoma 20q, que presenta una mutación en el gen (CHRNA4) de la subunidad 4 del receptor nicotínico de la acetilcolina. La segunda muestra una epilepsia lateral temporal autosómica dominante asociada al cromosoma 10q.Epilepsia idiopatikoen sorreran parte hartzen duten zenbait geneen isolaketak epilepsiaren sailkapena hobetzea baimendu du. Lan honetan sindrome epileptikoa duten bi sendiren ikerketa kliniko eta genetikoa aurkezten da. Lehenak, 20q kromosomari loturiko gau epilepsia frontala agertzen du, azetil kolinaren errezeptore nikotinikoaren 4 azpiunitatearen genean (CHRNA4) mutazio bat agertzen duelarik. Bigarrenak, 10q kromosomari loturiko autosomiko gainartzailea den epilepsia albo-tenporala agertzen du.L'isolement de certains gènes qui interviennent dans l'origine de l'épilepsie idiopathique a permis une meilleure classi cation de l'épilepsie. Dans ce travail on rend compte de l'examen clinique de deux familles qui souffrent du syndrome épileptique. La première montre une épilepsie nocturne associée au chromosome 20q, qui présente une mutation dans le gène (CHRNA4) de la sous-unité 4 du récepteur nicotinique de l'acétylcholine. La seconde montre une épilepsie latérale temporelle autosomique dominante associée au chromosome 10q.The isolating of certain genes that intervene in the origin of idiopathic epilepsy has allowed for a better classification of epilepsy as a whole. This work is about the clinical analysis of two families with an epileptic syndrome. The first family displays a nocturnal epilepsy associated to chromosome 20q, which has a mutation in gen (CHRNA4) of sub-unit á4 of the acetylcoline nicotinic receptor. The second family displays a dominant lateral temporal lobe and autosomal epilepsy associated to chromosome 10q

The LRRK2 G2019S mutation in a series of Argentinean patients with Parkinson's disease: Clinical and demographic characteristics

OBJECTIVES: To determine clinical characteristics and frequency of leucine-rich repeat kinase 2 gene (LRRK2) mutations in a cohort of patients with Parkinson's disease (PD) from Argentina. BACKGROUND: Variation in the LRRK2 gene represents the most common genetic determinant of PD, only few data are available from Latin-America. DESIGN/METHODS: Informed consent was obtained and all studies were approved by the Institutional Review Boards. Fifty five consecutive PD patients were recruited. A structured interview and neurological examination were used to collect demographic and clinical information. Blood samples were obtained and DNA extracted from patient venous blood. All LRRK2 exons from 25 exon to 51 exon were screened in all patients. RESULTS: Clinical and molecular data of 55 patients with PD were analyzed. Mean age was 68.8±10.6 years. Jewish and Basque ancestries were found positive in 9 and 7 patients, respectively; family history of PD was identified in 16 patients. The G2019S mutation was present in 3 Ashkenazi Jewish subjects (5.45%); all of them reported family history of PD in first-degree relatives. Although Argentina possesses one of the most important Basque communities outside Spain, non R1414G mutation was identified in this cohort. Eleven single polymorphisms (SNP) were identified in this cohort. The mean age at onset was higher in G2019S mutation carriers than non-carriers (66.67 vs 58.78 years). Asymmetrical tremor as initial symptom and non-motor symptoms occurred at similar frequencies in both groups. The G2019S mutation carriers showed a non significant increase in dyskinesias, and 2/3 developed Dopamine Dysregulation Syndrome and visual hallucinations. Systemic disorder identified in G2019S mutation carriers included: celiac disease, hypothyroidism, Hashimoto's Thyroiditis and arterial hypertension. CONCLUSIONS: The prevalence of LRRK2 G2019S mutation in this Argentinean cohort was similar to other international series, with a higher prevalence in Ashkenazi Jewish. The phenotype was indistinguishable from patients with idiopathic PD. Interestingly, we identified immune mediated disorders in two PD patients carrying the G2019S mutation. Within this context, recent studies have identified full-length LRRK2 as a relatively common constituent of many cell types in the immune system including human peripheral blood mononuclear cells. Nevertheless, a casual association could not be excluded and the analysis of more extensive series is required.Fil: Gatto, Emilia Mabel. Instituto de Neurociencias Buenos Aires S. A.; Argentina. Sanatorio de la Trinidad Mitre; ArgentinaFil: Parisi, Virginia. Sanatorio de la Trinidad Mitre; ArgentinaFil: Converso, Daniela Paola. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martí Massó, José Félix. Hospital Donostia; EspañaFil: Paisán Ruiz, Coro. Icahn School of Medicine at Mount Sinai; Estados Unido