Cruz, S; Schaefer, A; Joshi, A; Baker, M
Seixas, A; Loureiro, R; Costa, C; Ordóñez-Ugalde, A; Marcelino, H; Oliveira, L; Loureiro L, e outros
Advances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, but only five SCAs originate from non-coding mutations. Over half of SCA-affected families, however, remain without a genetic diagnosis. We used genome-wide linkage analysis, NGS, and repeat analysis to identify an (ATTTC)n insertion in a polymorphic ATTTT repeat in DAB1 in chromosomal region...
Santos, M; Cruz, S; Peres, J; Santos, L; Tavares, P; Basto, JP; Salgado, V; Valverde, A
DOK7 congenital myasthenic syndrome (DOK7-CMS) generally presents early in life and is treated with salbutamol or ephedrine. This report describes an atypical case of a 39-year-old woman who presented with proximal upper limb weakness in the third trimester of pregnancy and was initially diagnosed with seronegative myasthenia gravis. Dramatic clinical worsening under pyridostigmine and further inefficacy of steroids, intravenous human immunoglobulin (IVIG) and plasma exchange (PLEX) led to the presumptive diagnosis of a CMS. Initially, a slow-channel CMS was regarded as more probable due to prominent finger extension weakness. Accordingly, fluoxetine was started and a lengthy improvement was seen. Clinical...
Menezes, J; Ventura, C; Costa, J; Parreira, E; Romão, L
Our results prove that c.1871-14T>G is causative of type I PS deficiency, highlighting the importance of performing mRNA-based studies in order to evaluate variants pathogenicity. We evidence the increased risk of venous thromboembolism associated with this cryptic splice-site variant if present in patients with PS deficiency.
Ginestal, R; García-Moreno, E; Marques, J; Simões, R; Serafim, A; Palma, T
A paresia do motor ocular externo é a neuropatia intracraniana secundária à síndrome de hipotensão intracraniana mais frequentemente descrita (habitualmente espontânea ou iatrogénica, especialmente depois de punção lombar ou de anestesia epidural). Mesmo assim, trata-se duma complicação pouco frequentemente descrita na literatura. As lesões por facadas na medula espinhal são relativamente infrequentes, embora ainda mais infrequente é a sua apresentação clínica de forma atrasada. Apresentamos o caso de um homem de 31 anos de idade que começou com diplopia 6 dias depois de ser esfaqueado na região lombar. Este caso clínico mostra a necessidade duma avaliação precoce e eficaz da...
As miopatias genéticas são um grupo complexo de doenças neuromusculares. A crescente descrição de novas alterações genéticas e de novos genes candidatos diminui a validade das designações nosológicas prévias baseadas em fenótipos clínicos concretos promovendo, ao invés, a sua substituição por termos que identificam a disfunção de determinadas proteínas constituintes das fibras musculares e que frequentemente correspondem a espectros fenotípicos extensos. O reconhecimento de fenótipos está portanto a tornar-se progressivamente mais complexo, o que justifica um esforço de sistematização dos achados clínicos que inclua também elementos fornecidos por exames auxiliares de diagnóstico.
Este artigo propõe um conjunto de fluxogramas diagnósticos que...
Cruz, S; Figueroa-Bonaparte, S; Gallardo, E; de Becdelièvre, A; Gartioux, C; Allamand, V; Piñol, P; Garcia, MA; Jiménez-Mallebriera, C; Llauger, J; González-Rodríguez, L; Cortes-Vicente, E; Illa, I; Díaz-Manera, J
The classical phenotypes of collagen VI-associated myopathies are well described. Little is known, however, about the progression of patients at the mildest end of the clinical spectrum. In this report, we describe the clinical findings and the results of MRI, muscle biopsy, collagen VI expression in cultured skin fibroblasts and genetic tests of a series of patients with Bethlem myopathy. Our series highlights the existence of mild presentations of this disorder that progresses only slightly and can easily be overlooked. Analysis of the genetic studies suggests that missense mutations can be associated to a milder clinical presentation. Muscle MRI is...
Almeida, V; Conceição, I; Fineza, I; Coelho, T; Silveira, F; Santos, M; Valverde, A; Geraldo, A; Maré, R; Aguiar, TC; Mendonça, C; Martins, J; Medeiros, L; Barroso, C; Vieira, JP; Moreno, T; Negrão, L; Dias, M; Lacerda, L; Evangelista, T
Pompe disease is a rare metabolic disorder with available enzymatic replacement therapy. Contrasting with the classic infantile form, the others subtypes have a heterogeneous presentation that makes an early and accurate diagnosis difficult. We conducted a prospective, multicenter, observational study to identify undiagnosed patients. During a one-year period, patients followed in Portuguese neuromuscular outpatient clinics with proximal muscle weakness affecting upper and/or lower limbs, hyperCKemia in two or more determinations or hypotonia and hyperCKemia, were screened for acid α-glucosidase deficiency by dried blood spots. Lysosomal acid-alpha-1,4-glucosidase activity was determined by tandem mass spectrometry and positive results were confirmed by molecular...
Cruz, S; Taipa, R; Nogueira, C; Pereira, C; Almeida, S; Neiva, R; Geraldes, T; Guimarães, A; Melo-Pires, M; Vilarinho, L
Mitochondrial disorders display remarkable genetic and phenotypic heterogeneity.
We performed a retrospective analysis of the clinical, histological, biochemical, and genetic features of 65 patients with molecular diagnoses of mitochondrial disorders.
The most common genetic diagnosis was a single large-scale mitochondrial DNA (mtDNA) deletion (41.5%), and the most frequent clinical phenotype was chronic progressive external ophthalmoplegia (CPEO). It occurred in 41.5% of all patients, primarily in those with mtDNA deletions. Histological signs of mitochondrial dysfunction were found in 73.8% of patients, and respiratory chain enzyme assay (RCEA) abnormalities were detected in 51.9%.
This study confirms the high relative frequency of single large-scale deletions among...
Santos, M; Cruz, S; Casimiro, C; Biscoito, M; Costa, M
La asociación MURCS (OMIM 60176), también conocida como síndrome de Mayer-RokitanskyKüster-Hauser de tipo II, constituye una rara malformación que afecta aproximadamente a una de cada 50.000 mujeres [1,2]. Consiste en la combinación de aplasia de los conductos de Müller, aplasia o ectopia renal unilateral y displasia de los somitas cervicodorsales, relacionado con deformidades vertebrales del espectro
Klippel-Feil, y asociado o no a malformaciones occipitoatloideas . La disección de la arteria vertebral es una causa poco frecuente de ictus, que puede asociarse a anomalías del desarrollo craneocervical . Se describe un caso de ictus causado por disección de la arteria vertebral en...
Peres, J; Cruz, S; Oliveira, R; Santos, L; Valverde, A
A 68-year-old Caucasian female was admitted to the emergency department with a progressive history of behavioural symptoms and anxiety followed by visual and auditory hallucinations, forgetfulness, and impaired gait in the previous 3 months. On examination she was psychotic and had a postural and rest tremor of the upper limbs, cogwheel rigidity of the four limbs, retropulsion on standing position, and inability to walk. During the following 2 weeks she developed xerostomia and unilateral parotiditis that improved with steroids. A simultaneous improvement of the cognitive abilities allowed for the detection of sensory ataxia of the lower limbs. Sensory ganglionopathy was...
Pina, S; Pedrosa, C; Feijóo, B; Machado, S; Prieto, I; Costa, C; Santos, MJ
The authors report the case of a child with horizontal gaze palsy with progressive scoliosis and keratoconus. ROBO3 analysis identified compound heterozygous mutations. Keratoconus surgical approach resulted in visual acuity improvement in both eyes. The previously unreported occurrence of keratoconus with horizontal gaze palsy with progressive scoliosis suggests that ophthalmologic assessment should search for signs of this ectasia in these patients.
Sousa, D; Ferro, J; Canhão, P; Barinagarrementeria, F; Bousser, MG; Stam, J; Pinto, A; Baptista, M; Béjot, Y; Dequatre-Poncelle, N
Isolated posterior fossa parenchymal lesions associated with cerebral venous thrombosis (CVT) are rare. Posterior fossa lesions are an independent predictor of death in CVT. We aim to describe the characteristics and outcome of patients with CVT and isolated posterior fossa lesions and assess the safety of anticoagulation in patients with posterior fossa lesions associated with CVT.
We retrieved data from all patients with posterior fossa parenchymal lesions in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort related to clinical features, therapy and outcome. Fisher's exact test was used to evaluate associations. To assess the safety of anticoagulation...
Ribeiro, R; Ferreira, M; Simões, H; Parreira, E
A paralisia periódica hipocaliémica é uma complicação neurológica do hipertiroidismo, especialmente na doença de Graves, rara em não asiáticos. Caracteriza-se por episódios auto-limitados recorrentes de fraqueza muscular que afecta sobretudo os músculos proximais dos membros inferiores. Acompanha-se de hipocaliémia, potencialmente grave.
Apresenta-se o caso de um doente de 39 anos, caucasiano, com doença de Graves, medicado com carbimazol. Durante
3 meses, teve episódios recorrentes de tetraparésia de predomínio proximal, de curta duração, que surgiam após períodos
de repouso, motivo pelo qual foi internado. Por manter episódios de agravamento da tetraparésia, associados a hipocaliémia e hipomagnesiémia, e por, laboratorialmente, apresentar hipertiroidismo, admitiu-se...
Hupperts, R; Becker, V; Friedrich, J; Gobbi, C; Salgado, AV; Sperling, B; You, X
The 12-month observational PERSIST study (NCT01405872) evaluated adherence associated with the intramuscular IFNβ-1a (i.m. IFN-β-1a) autoinjector pen in multiple sclerosis (MS) patients.
MS patients initiating i.m. IFN-β-1a autoinjector treatment were prospectively assessed for physician-reported persistence (percentage of patients remaining on therapy) and patient-reported outcomes, including adherence (percentage of unmissed injections), compliance (percentage of patients missing no injections), tolerability (injection-site reactions [ISRs] and pain) and satisfaction.
The intent-to-treat population included 232 patients; of the 188 physician-reported 12-month completers, 182 patients remained on treatment (96.8% persistence). Monthly compliance rates were 87.5 - 96.2%. Mean monthly pain scores were 1.5 - 1.8 (scale: 0 =...
Costa, S; Suárez-Calvet, M; Antón, S; Dols-Icardo, O; Clarimón, J; Alcolea, D; Fortea, J; Carmona, M; Sala, I; Sánchez-Saudinós, MB; Blesa, R; Lleó, A
The aim of this study was to compare the applicability of the 1998 consensus diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD) with the recently proposed diagnostic criteria of the International bvFTD Criteria Consortium (FTDC).
We reviewed each individual item in the 1998 and FTDC criteria in 30 patients with bvFTD followed in a memory clinic (including 2 with the C9orf72 gene repeat expansion).
All patients fulfilled the FTDC criteria (40% possible, 60% probable bvFTD) but only 66.7% fulfilled the 1998 criteria. One of the C9orf72 expansion carriers did not fulfill the 1998 criteria. This discordance was always due to...
Carvalho, A; Veiga, A; Morgado, J; Tojal, R; Rocha, S; Vale, J; Sa, MJ; Timoteo, A
INTRODUCTION. Multiple sclerosis (MS) is a disabling disease occurring mainly in women of childbearing age. MS may interfere with family planning and motherhood decision. AIM. To study the influence of MS diagnosis and course of the disease on motherhood decision. PATIENTS AND METHODS. The cohort of 35 to 45-year-old female patients diagnosed with MS for at least ten years was selected from six Portuguese MS centers. A structured questionnaire was applied to all patients in consecutive consultation days. Clinical records were reviewed to characterize and collect information about the disease and pregnancies. RESULTS. One hundred women were included; mean age...
Jonet, M; Maia, R; Santos, M
A hipoglicémia, situação clínica comum e muitas vezes auto-limitada, é a emergência metabólica e endócrina mais fre-
quente na prática clínica. O caso apresentado reporta-se a um homem de 31 anos, com hábitos alcoólicos acentuados, trazido
ao serviço de urgência por crise convulsiva tónico-clónico generalizada após três dias de jejum alimentar, mantendo ingestão
alcoólica abundante. À admissão pontuava 6 na escala de Glasgow, apresentava-se em estado pós-crítico e a glicémia capilar
era 21mg/dL. A tomografia computorizada crânio-encefálica mostrou edema cerebral difuso; iniciaram-se correcção da
glicémia e medidas anti-edema. O estudo complementar (avaliação analítica completa, electro-encefalograma e ressonância
magnética crânio-encefálica) confirmou o...
Crespo, A; Silva, B; Marques, L; Marcelino, E; Maruta, C; Costa, S; Timóteo, A; Vilares, A; Couto, F; Faustino, P; Correia, AP; Verdelho, A; Porto, G; Guerreiro, M; Herrero, A; Costa, C; Mendonça, A; Costa, L; Martins, M
Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD,...
Fidalgo, P; Ahmed, M; Meyer, S; Lien, D; Weinkauf, J; Cardoso, F; Jackson, K; Bagshaw, S
BACKGROUND:Acute kidney injury (AKI) is a serious complication following lung transplantation (LTx). We aimed to describe the incidence and outcomes associated with AKI following LTx.
A retrospective population-based cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. The primary outcome was AKI, defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, in the first 7 post-operative days. Secondary outcomes included risk factors, utilization of renal replacement therapy (RRT), occurrence of post-operative complications, mortality and kidney recovery.
Of 445 LTx recipients included, AKI occurred in 306 (68.8%), with severity classified as...