Bases Clínicas e Laboratoriais para o Diagnóstico e Compreensão das Doenças Metabólicas Neonatais

The authors divide neonatal metabolic diseases into two major groups: intoxication and energy deficiency. The main signs which allow for the suspicion of the diagnosis are indicated for each group. The complementary examinations to be carried out by the Clinical Pathology Service of the Central Hospital and those which must be carried out by the metabolic diseases Reference Centre are reviewed. Based on the clinical framework and on the examination results, the authors establish five syndromatic groups to orientate diagnosis. The authors conclude by presenting differential diagnosis tables based on the original systematic classification by Jean-Marie Saudubray, with up-dated modifications from their own experience.

Does Metabolic Syndrome Predict Significant Angiographic Coronary Artery Disease?

INTRODUCTION: Metabolic syndrome (MS) is an independent predictor of acute cardiovascular events. However, few studies have addressed the relationship between MS and stable angiographic coronary artery disease (CAD), which has a different pathophysiological mechanism. We aimed to study the independent predictors for significant CAD, and to analyze the impact of MS (by the AHA/NHLBI definition) on CAD. METHODS: We prospectively included 300 patients, mean age 64±9 years, 59% male, admitted for elective coronary angiography (suspected ischemic heart disease), excluding patients with known cardiac disease. All patients underwent assessment of demographic, anthropometric, and laboratory data and risk factors, and subsequently underwent coronary angiography. RESULTS: In the study population, 23.0% were diabetic, 40.5% had MS (and no diabetes) and 36.7% had neither diagnosis. Significant CAD was present in 51.3% of patients. CAD patients were older and more frequently male and diabetic, with increased triglycerides and glucose and lower HDL cholesterol. Abdominal obesity was also less prevalent. MS was not associated with the presence of CAD (OR 0.94, 95% CI 0.59-1.48, p=0.778). Of the MS components, the most important predictors of CAD were increased glucose and triglycerides. Abdominal obesity was associated with a lower risk of CAD. In a multivariate logistic regression model for CAD, independent predictors of CAD were age, male gender, glucose and triglycerides. Body mass index had a protective effect. CONCLUSIONS: Although MS is associated with cardiovascular events, the same was not found for stable angiographically proven CAD. Age, gender, diabetes and triglycerides are the most influential factors for CAD, with abdominal obesity as a protective factor.

Prevalence of Metabolic Syndrome and Diabetes on a High-Risk Population with Suspected Coronary Artery Disease

Objectivos: A prevalência de Sindroma Metabólica (SM) e diabetes é variável consoante a definição utilizada, assim como com a região geográfica e o grupo étnico estudado. Não existem estudos em indivíduos portugueses com suspeita de doença arterial coronária. Analisámos a prevalência de SM e diabetes nesta população específica de doentes, comparando também definições. Métodos: Incluíram-se no estudo 300 indivíduos, com uma idade media de 64 ± 9 anos, 59% do género masculino, admitidos para angiografia coronária electiva, tendo sido excluídos os doentes com doença cardíaca previamente conhecida. Avaliou-se a prevalência de SM e de diabetes. Resultados: A prevalência ajustada de SM foi de 39,3% (critério NCEP-ATP III), 53,8% (critério IDF) e 48,4% (critério AHA/NHLBI). A prevalência ajustada de diabetes foi de 14,8% pela definição prévia da ADA e de 36.4% com a definição mais recente. A concordância global entre as definições de SM foi de 45,3%, sendo mais elevada entre as definições da AHA/NHLBI e da NCEP-ATP III (Kappa 0,821). A prevalência de SM está altamente dependente da idade em ambos os géneros, sendo mais prevalente no género feminino. A prevalência de diabetes é também dependente da idade, sendo semelhante em ambos os géneros. O componente de SM mais frequente é a hipertensão arterial, seguido pela obesidade abdominal, elevação da glicose, colesterol-HDL baixo e finalmente elevação dos triglicéridos. É também importante referir que 60% dos doentes estavam sob terapêutica hipolipemiante (56,6% com estatinas, 1,7% com fibratos e 1,7% com ambos). A diferença mais significativa entre géneros no que diz respeito aos componentes de SM é a elevada prevalência de obesidade abdominal no género feminino. Conclusões: Nesta população de alto risco, a prevalência de SM é elevada, sendo contudo a prevalência de diabetes semelhante à registada em estudos epidemiológicos na população geral.

Analysis of Synaptic Proteins in the Cerebrospinal Fluid as a New Tool in the Study of Inborn Errors of Neurotransmission

Abstract In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiological and diagnostic purposes in investigation of inherited disorders of neurotransmission. Dopamine receptor type 2 (D2R), dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were analysed in CSF samplesfrom 30 healthy controls (11 days to 17 years) by western blot analysis. Because VMAT2 was the only protein with intracellular localisation, and in order to compare results, GABA vesicular transporter, which is another intracellular protein, was also studied. Spearman’s correlation and Student’s t tests were applied to compare optical density signals between different proteins. All these synaptic proteins could be easily detected and quantified in the CSF. DAT, D2R and GABA VT expression decrease with age, particularly in the first months of life, reflecting the expected intense synaptic activity and neuronal circuitry formation. A statistically significant relationship was found between D2R and DAT expression, reinforcing the previous evidence of DAT regulation by D2R. To our knowledge, there are no previous studies on human CSF reporting a reliable analysis of these proteins. These kinds of studies could help elucidate new causes of disturbed dopaminergic and gabaergic transmission as well as understanding different responses to L-dopa in inherited disorders affecting dopamine metabolism. Moreover, this approach to synaptic activity in vivo can be extended to different groups of proteins and diseases.

Epidemiology of Asthma and Allergic Diseases in Portuguese Speaking Regions

The application of the same epidemiological methods in different countries allows important comparisons between different races and cultures. During the last decade, two large multi-centres epidemiological studies, the Portuguese Study of Allergic Diseases in Childhood (PAC study) and the International Study of Asthma and Allergies in Childhood (ISAAC study), were implemented in Portuguese speaking regions. The main objectives were to assess and compare allergic diseases prevalence. The authors stress out the significant differences observed in schoolchildren from the three continents, with different genetic and environmental background. It was found an increase trend in the prevalence of all allergic diseases, mainly rhinitis, in last decade. Rhinitis has been identified as an independent risk factor for asthma in Caucasian population.

Thoracic Manifestations of Connective Tissue Diseases

Connective tissue diseases (CTDs) comprise several immunologic systemic disorders, each of which associated with a particular set of clinical manifestations and autoimmune profile. CTDs may cause numerous thoracic abnormalities, which vary in frequency and pattern according to the underlying disorder. The CTDs that most commonly involve the respiratory system are progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, polymyositis, dermatomyositis, and mixed connective tissue disease. Pulmonary abnormalities in this group of patients may result from CTD-related lung disease or treatment complications, namely drug toxicity and opportunistic infections. The most important thoracic manifestations of CTDs are interstitial lung disease and pulmonary arterial hypertension, with nonspecific interstitial pneumonia being the most common pattern of interstitial lung disease. High-resolution computed tomography is a valuable tool in the initial evaluation and follow-up of patients with CTDs. As such, general knowledge of the most common high-resolution computed tomographic features of CTD-related lung disease allows the radiologist to contribute to better patient management.

Non-Progressive Leukoencephalopathy with Bilateral Temporal Cysts

We report two cases of a peculiar leukoencephalopathy with temporal cysts. Both patients have a non-progressive neurological disorder with mental retardation, microcephaly and sensorineural deafness although clinical differences between them may reflect a different aetiology. The metabolic disorders with white matter involvement and the recently described leukoencephalopathies (Van Der Knaap disease, 'vanishing white matter disease') were excluded based on clinical, biologic and imaging findings. Cytomegalovirus infection is a likely possibility in the first case although the magnetic resonance imaging picture is only partially similar to previously reported cases. Our patients are strikingly similar to the patients reported by Deonna et al. and Olivier et al. We discuss the clinical and imaging findings in our patients and the differential diagnosis considering the known disorders of the white matter in childhood.

Distribution and Etiology of Chronic Respiratory Diseases in Primary Healthcare Departments in Cape Verde

Data on chronic respiratory diseases (CRD) are scarce or unavailable in most African countries. We aimed to determine the prevalence of CRD and associated risk factors in Cape Verde, at the primary healthcare level.

Under-Report and Underdiagnosis of Chronic Respiratory Diseases in an African Country

BACKGROUND: Chronic respiratory diseases (CRD) are greatly underestimated. The aim of this study was to assess the burden associated with reported CRD and chronic obstructive pulmonary disease, as defined on the basis of various standardized criteria, by estimating their point prevalence in a sample of individuals attending the Primary Health Care (PHC) level and Emergency Room (ER) Departments in Cape Verde (CV) archipelago. The second aim of the study was to identify factors related to airways obstruction and reported CRD in this population. METHODS: A cross-sectional study was carried out in CV during 2 weeks. Outpatients aged more than 20 years seeking care at PHC level and ER answered a standardized questionnaire and were subjected to spirometry, independently of their complaint. Two criteria for airways obstruction were taken into account: forced expiratory volume (FEV(1)) <80% of the predicted value and FEV(1)/forced vital capacity (FVC) ratio <0.70. RESULTS: A total of 274 individuals with a satisfactory spirometry were included. 22% of the individuals had a FEV(1) < 80%. Individuals older than 46 years had a higher risk of having airways obstruction. Asthma diagnosis (11%) had a clear association with airways obstruction. Smoking was a risk factor for a lower FEV(1). Working in a dust place and cooking using an open fire were both related to chronic bronchitis and asthma diagnosis. CONCLUSION: Under-report and underdiagnosis of chronic respiratory conditions seem to be a reality in CV just as in other parts of the world. To improve diagnosis, our results reinforce the need of performing a spirometry

Recommendations for Vaccination in Adult Patients with Systemic Inflammatory Rheumatic Diseases from the Portuguese Society of Rheumatology

Serious infections are a major cause of morbidity and mortality in systemic inflammatory rheumatic disease (SIRD) patients. Although vaccination may prevent numerous infections, vaccination uptake rates are low in this group of patients. OBJECTIVES: To develop evidence-based recommendations for vaccination in SIRD patients. METHODS: We searched MEDLINE (until 31 October 2014) and EMBASE (until 14 December 2014) databases, as well as the ACR and EULAR congress abstracts (2011-2014). Patients with any systemic inflammatory rheumatic disease were included and all vaccines were considered. Any safety and efficacy outcomes were admitted. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Data were subsequently pooled according to the type of vaccine and the SIRD considered. Results were presented and discussed by a multidisciplinary panel and systematic literature review (SLR)-derived recommendations were voted according to the Delphi method. The level of agreement among rheumatologists was assessed using an online survey. RESULTS: Eight general and seven vaccine-specific recommendations were formulated. Briefly, immunization status should routinely be assessed in all SIRD patients. The National Vaccination Program should be followed and some additional vaccines are recommended. To maximize the efficacy of vaccination, vaccines should preferably be administered 4 weeks before starting immunosuppression or, if possible when disease activity is controlled. Non-live vaccines are safe in SIRD, including immunosuppressed patients. The safety of live attenuated vaccines in immunosuppressed patients deserves further ascertainment, but might be considered in particular situations. DISCUSSION: The present recommendations combine scientific evidence with the multidisciplinary expertise of our taskforce panel and attained desirable agreement among Portuguese rheumatologists. Vaccination recommendations need to be updated on a regular basis, as more scientific data regarding vaccination efficacy and safety, emergent infectious threats, new vaccines as well as new immunomodulatory therapies become available.

Undetectable Levels of CSF Amyloid-β Peptide in a Patient with 17β-Hydroxysteroid Dehydrogenase Deficiency

17β-hydroxysteroid dehydrogenase 10 (HSD10) deficiency is a rare X-linked inborn error of isoleucine catabolism. Although this protein has been genetically implicated in Alzheimer's disease pathogenesis, studies of amyloid-β peptide (Aβ) in patients with HSD10 deficiency have not been previously reported. We found, in a severely affected child with HSD10 deficiency, undetectable levels of Aβ in the cerebrospinal fluid, together with low expression of brain-derived neurotrophic factor, α-synuclein, and serotonin metabolites. Confirmation of these findings in other patients would help elucidating mechanisms of synaptic dysfunction in this disease, and highlight the role of Aβ in both early and late periods of life.