Browsing by Author "Santos, Helena"
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- Assessing Lysosomal Disorders in the NGS Era: Identification of Novel Rare VariantsPublication . Encarnação, Marisa; Coutinho, Maria Francisca; Silva, Lisbeth; Ribeiro, Diogo; Ouesleti, Souad; Campos, Teresa; Santos, Helena; Martins, Esmeralda; Cardoso, Maria Teresa; Vilarinho, Laura; Alves, SandraLysosomal storage diseases (LSDs) are a heterogeneous group of genetic disorders with variable degrees of severity and a broad phenotypic spectrum, which may overlap with a number of other conditions. While individually rare, as a group LSDs affect a significant number of patients, placing an important burden on affected individuals and their families but also on national health care systems worldwide. Here, we present our results on the use of an in-house customized next-generation sequencing (NGS) panel of genes related to lysosome function as a first-line molecular test for the diagnosis of LSDs. Ultimately, our goal is to provide a fast and effective tool to screen for virtually all LSDs in a single run, thus contributing to decrease the diagnostic odyssey, accelerating the time to diagnosis. Our study enrolled a group of 23 patients with variable degrees of clinical and/or biochemical suspicion of LSD. Briefly, NGS analysis data workflow, followed by segregation analysis allowed the characterization of approximately 41% of the analyzed patients and the identification of 10 different pathogenic variants, underlying nine LSDs. Importantly, four of those variants were novel, and, when applicable, their effect over protein structure was evaluated through in silico analysis. One of the novel pathogenic variants was identified in the GM2A gene, which is associated with an ultra-rare (or misdiagnosed) LSD, the AB variant of GM2 Gangliosidosis. Overall, this case series highlights not only the major advantages of NGS-based diagnostic approaches but also, to some extent, its limitations ultimately promoting a reflection on the role of targeted panels as a primary tool for the prompt characterization of LSD patients.
- Eating disorder - a diagnosis of exclusionPublication . Fonseca, Margarida Silva; Santos, Helena; Guedes, Raquel; Tavares, Hugo BragaIn adolescents with weight loss, diagnoses other than eating disorders should be considered, namely neurological diseases. A 16-year-old girl with an intellectual development disorder was referred to the Adolescent Medicine outpatient clinic from Child Psychiatry with a diagnosis of eating disorder and persistent anemia. Her body mass index was consistently below the fifth percentile and long-lasting eating difficulties were reported since the age of 15. The girl had no other gastrointestinal, articular, or respiratory complaints, neither polyuria, polydipsia, or recurrent fever. Parental divorce and domestic violence were reported. The patient complained of excessive daytime sleepiness, asthenia, intermittent myalgia, and muscular weakness episodes. Phenotypic characteristics and personal medical history led to clinical suspicion of a neuromuscular disease and genetic study confirmed myotonic dystrophy type 1. This case highlights the importance of considering other diagnoses besides eating disorders in adolescents with eating problems. An exhaustive evaluation of personal and family medical history, patient complaints, and detailed physical examination is mandatory.
- Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic EraPublication . Baldo, Manuela Schubert; Nogueira, Célia; Pereira, Cristina; Janeiro, Patrícia; Ferreira, Sara; Lourenço, Charles M.; Bandeira, Anabela; Martins, Esmeralda; Magalhães, Marina; Rodrigues, Esmeralda; Santos, Helena; Ferreira, Ana Cristina; Vilarinho, LauraMitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.