Fetal Inferior Vena Cava Thrombosis Associated With Non-Immune Hydrops Fetalis and Maternal Mirror Syndrome.

Prenatal assessment of the inferior vena cava (IVC) should be considered in pregnancies with atypical presentations of fetal ascites and placentomegaly. We examine a case of a 25-year-old gravida 2 para 1 type 1 diabetic female at 29 and 4/7 weeks' gestation. Ultrasound (US) showed fetal ascites and placentomegaly with increased middle cerebral artery peak systolic velocity (MCA-PSV) suspicious of fetal anemia. Cordocentesis with intrauterine transfusion briefly resolved the fetal ascites, though the mother developed pulmonary edema and pleural effusion, suggestive of mirror syndrome. On US, fetal ascites returned and progressed to non-immune hydrops fetalis, prompting delivery. Neonatal US revealed a heterogenous and calcified thrombus within the IVC.

Pharmacologic inhibition of N-linked glycan trimming with kifunensine disrupts GLUT1 trafficking and glucose uptake.

The facilitative glucose transport GLUT1 (SLC2A1) is a constitutively expressed membrane protein involved in basal uptake of blood glucose. GLUT1 modification by N-linked glycosylation at a single asparagine residue (N45) appears to play multiple roles in the trafficking, stability and transport activity of this protein. Here we examine the role of complex N-glycosylation on GLUT1 function in renal epithelial cells by arresting this modification at the high-mannose stage with the mannosidase I inhibitor kifunensine. Consistent with prior work in which GLUT1 glycosylation was completely inhibited, we find that kifunensine treatment results in a time-dependent decrease of up to 40% in cellular glucose uptake. We further demonstrate that this effect is primarily a result of deficient GLUT1 trafficking to the cell membrane due to quality control mechanisms that instead direct GLUT1 to the ER-associated degradation (ERAD) pathway. Unlike tunicamycin, which inhibits the first step in N-glycosyl transfer and causes dramatic cell cycle arrest, kifunensine causes only a modest decrease in GLUT1 levels and cell cycle progression in both normal and transformed renal cells. The effect of kifunensine on the cell cycle appears to be independent of its effect on GLUT1, since all renal cell types in this study displayed decreased proliferation regardless of their dependence on glucose uptake for growth and survival. Together these results indicate that proper N-glycan processing plays an important role in directing GLUT1 to the cell surface and that disruption of mannosidase activity results in aberrant degradation of GLUT1 by the ERAD pathway.