Case report: Diagnosis of a patient with Sifrim–Hitz–Weiss syndrome, development and epileptic encephalopathy-14, and medium chain acyl-CoA dehydrogenase deficiency

BackgroundIt is generally recognized that genetic metabolic disorders can result in neurological symptoms such as seizures, developmental delay, and intellectual disability. Heterogeneous clinical presentations make the diagnosis challenging.Case presentationIn this case report, we present a unique and complex genetic disorder observed in a female patient who exhibited three pathogenic gene variants in the KCNT1, ACADM, and CHD4 genes. The convergence of these variants resulted in a multifaceted clinical presentation characterized by severe seizures of combined focal and generalized onset, metabolic dysfunction, and neurodevelopmental abnormalities. The identification and functional characterization of these gene variants shed light on the intricate interplay between these genes and the patient's phenotype. EEG revealed an epileptiform abnormality which presented in the inter-ictal period from the left frontal-central area and in the ictal period from the left mid-temporal area. The brain MRI revealed volume loss in the posterior periventricular area and parietal parenchyma, myelin destruction with no sign of hypoxic involvement, and left dominant enlargement of the lateral ventricles secondary to loss of central parenchyma. The patient was diagnosed through exome sequencing with Sifrim–Hitz–Weiss syndrome, development and epileptic encephalopathy-14, and medium-chain acyl-CoA dehydrogenase deficiency. An antiseizure medication regimen with valproic acid, levetiracetam, phenobarbital, and clonazepam was initiated. However, this led to only partial control of the seizures.ConclusionClinical follow-up of the patient will further define the clinical spectrum of KCNT1, ACADM, and CHD4 gene variants. It will also determine the long-term efficacy of the treatment of seizures and the development of precision medicine for epilepsy syndromes due to gain-of-function variants. Special emphasis should be put on the role and importance of large-scale genomic testing in understanding and diagnosing complex phenotypes and atypical epileptic syndromes

The impact of type of dietary protein, animal versus vegetable, in modifying cardiometabolic risk factors: A position paper from the International Lipid Expert Panel (ILEP)

Proteins play a crucial role in metabolism, in maintaining fluid and acid-base balance and antibody synthesis. Dietary proteins are important nutrients and are classified into: 1) animal proteins (meat, fish, poultry, eggs and dairy), and, 2) plant proteins (legumes, nuts and soy). Dietary modification is one of the most important lifestyle changes that has been shown to significantly decrease the risk of cardiovascular (CV) disease (CVD) by attenuating related risk factors. The CVD burden is reduced by optimum diet through replacement of unprocessed meat with low saturated fat, animal proteins and plant proteins. In view of the available evidence, it has become acceptable to emphasize the role of optimum nutrition to maintain arterial and CV health. Such healthy diets are thought to increase satiety, facilitate weight loss, and improve CV risk. Different studies have compared the benefits of omnivorous and vegetarian diets. Animal protein related risk has been suggested to be greater with red or processed meat over and above poultry, fish and nuts, which carry a lower risk for CVD. In contrast, others have shown no association of red meat intake with CVD. The aim of this expert opinion recommendation was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing protein intake, especially plant-based proteins and certain animal-based proteins (poultry, fish, unprocessed red meat low in saturated fats and low-fat dairy products) have a positive effect in modifying cardiometabolic risk factors. Red meat intake correlates with increased CVD risk, mainly because of its non-protein ingredients (saturated fats). However, the way red meat is cooked and preserved matters. Thus, it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products (especially whey protein) are inversely correlated to hypertension, obesity and insulin resistance

Clinical Decision-Making for Heart Failure in Kosovo: A Conjoint Analysis

Background: Heart failure represents a life-threatening progressive condition. Early diagnosis and adherence to clinical guidelines are associated with improved outcomes for patients with heart failure. However, adherence to clinical guidelines remains limited in Kosovo. Objective: To assess the clinical decision-making related to heart failure diagnosis by evaluating clinicians’ preferences for clinical attributes. Method: Conjoint analysis with 33 clinical scenarios with physicians employed in public hospitals in Kosovo. Setting: Two public hospitals in Kosovo that benefited from quality improvement intervention. Participants: 14 physicians (internists and cardiologists) in two hospitals in Kosovo. Outcome measures: The primary outcome was the overall effect of clinical attributes on the decision for heart failure diagnosis. Results: When considering clinical signs, the likelihood of a heart failure diagnosis increased for ages between 60 to 69 years old (RRR, 1.88; CI 95%, 1.05–3.34) and a stable heart rate (RRR, 1.93; CI 95%, 1.05–3.55) and decreased for the presence of edema (RRR, 0.23; CI 95%, 0.15–0.36), orthopnea (RRR, 0.31; CI 95%, 0.20–0.48), and unusual fatigue (RRR, 0.61; CI 95%, 0.39–0.94). When considering clinical examination findings, the likelihood for heart failure diagnosis decreased for high jugular venous pressure (RRR, 0.49; CI 95%, 0.32–0.76), pleural effusion (RRR, 0.35; CI 95%, 0.23–0.54), hearing third heart sound, (RRR, 0.50; CI 95%, 0.33–0.77), heart murmur (RRR, 0.57; CI 95%, 0.37–0.88), troponin levels (RRR, 0.59; CI 95%, 0.38–0.91), and NTproBNP levels (RRR, 0.36; CI 95%, 0.24–0.56). Conclusions: We often found odd and wide variations of clinical signs and examination results influencing the decision to diagnose a person with heart failure. It will be important to explore and understand these results better. The study findings are important for existing quality improvement support efforts and contribute to the standardization of clinical decision-making in the public hospitals in the country. This experience and this study can provide valuable impetus for further examination of these efforts and informing policy and development efforts in the standardization of care in the country