Search

Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway.

Introdução: A elevada prevalência de obesidade infantil em Portugal é considerada uma das grandes epidemias do século XXI. Empiricamente, o aleitamento materno é apontado, pelos seus reconhecidos benefícios na saúde do lactente e da mãe, como um fator protetor ao desenvolvimento de obesidade infantil. No entanto, são necessários mais estudos que demonstrem esta relação. Materiais e métodos: Realizámos uma revisão sistemática da literatura com o objetivo de aferir o papel do aleitamento materno na prevenção da obesidade infantil. Mais concretamente, pesquisámos evidência científica acerca da relação entre as duas variáveis supracitadas, assim como os mecanismos potencialmente envolvidos nesta associação. Analisámos artigos científicos publicados em revistas indexadas de diversos países, compreendidos entre 01.01.2014 e 31.12.2016. O seu acesso adveio de bases de dados internacionais e de idoneidade reconhecida. Resultados: Na maioria dos estudos revistos, verificámos que o aleitamento materno apresenta uma relação de proteção com a obesidade infantil; no entanto, em alguns estudos, não foi encontrada qualquer associação entre as duas variáveis. A leptina e o cortisol foram sugeridos como intervenientes nos mecanismos potencialmente envolvidos na relação referida. Discussão e conclusão: O aleitamento materno apresenta um papel protetor sobre a obesidade infantil, nomeadamente aquando de uma duração superior a 6 meses e em exclusivo. O efeito protetor referido pode estender-se a longo prazo. A questão relativa aos mecanismos envolvidos nesta associação merece uma investigação mais aprofundada.

Introduction: Stevens-Johnson Syndrome (SJS) is a rare mucocutaneous disease whose incidence increases with age and about 20% of cases occur in children and adolescents. Mortality reaches 5%. Case description: We present a male adolescent, 11 years old, admitted due to oral mucosa erosions, lips edema and erythema, enanthema, cutaneous target lesions and edemaciate, erythematous and exudative glans, treated with non-steroidal anti-inflammatory drugs one day before the onset of cutaneous symptoms. The diagnostic tests didn’t show alterations and microbiological tests and serologies were negative. The patient was admitted to the Pediatrics Department with diagnosis of SJS. He was hospitalized for 10 days with intravenous analgesia, mucositis solution and topical emollient, hydric and nutritional reinforcement. He exhibited successive improvement of lesions with complete resolution after 2 weeks. Conclusions: The diagnosis of SJS is clinical, with special emphasis to the use of drugs or the presence of previous infection. Its recognition is important so that clinical intervention can occur as early as possible, decreasing the likelihood of complications and death.