Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures.

Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a 'preeclampsia-like syndrome'. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. Methods: We utilised whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n = 9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS-CoV-2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS-CoV-2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.

Case report: is low α-Gal enzyme activity sufficient to establish the diagnosis of Fabry disease?

Fabry disease is an X-linked lysosomal storage disease due to alpha-galactosidase A (α-Gal A) deficient activity which leads to the accumulation of glucoesphingolipids, such as globotriaosilceramide. There are over 700 known mutations of the enzyme gene, and most of them cause Fabry Disease. This case report describes a hemodialysis patient with a rare and controversial GLA gene mutation, the D313Y. The medecial investigation confirmed that D313Y is an alpha-galactosidase A sequence variant that causes pseudo deficient enzyme activity in plasma but not Fabry disease. Thus, clinical symptoms that prompted Fabry disease investigation could not be attributable to Fabry disease and therefore enzyme replacement therapy was not indicated.

Case report: is low α-Gal enzyme activity sufficient to establish the diagnosis of Fabry disease? / Relato de caso: a diminuição da enzimaα-Gal l é suficiente para estabelecer o diagnóstico?

Abstract Fabry disease is an X-linked lysosomal storage disease due to alpha-galactosidase A (α-Gal A) deficient activity which leads to the accumulation of glucoesphingolipids, such as globotriaosilceramide. There are over 700 known mutations of the enzyme gene, and most of them cause Fabry Disease. This case report describes a hemodialysis patient with a rare and controversial GLA gene mutation, the D313Y. The medecial investigation confirmed that D313Y is an alpha-galactosidase A sequence variant that causes pseudo deficient enzyme activity in plasma but not Fabry disease. Thus, clinical symptoms that prompted Fabry disease investigation could not be attributable to Fabry disease and therefore enzyme replacement therapy was not indicated.

Resumo Doença de Fabry (DF) é uma doença de depósito lisossômico ligada ao cromossomo X, causada pela deficiência da enzima alfa-galactosidase A (α-Gal A) que leva ao acúmulo de glicoesfingolipídeos, principalmente globotriaosilceramide. Existem mais de 700 mutações conhecidas do gene da enzima, a maioria delas são causadoras de DF. Este relato de caso descreve sobre um paciente em hemodiálise com uma mutação do gene GLA rara e controversa, a D313Y. A investigação médica confirmou que D313Y é uma variante que leva à pseudodeficiência plasmática da enzima, mas não ocasiona DF. Assim, os sintomas clínicos que induziram a investigação da doença não devem ser atribuídos à DF e, portanto, não foi indicada a terapia de reposição enzimática.