ABSTRACT
Although toxicity from excessive exogenous vitamin D supplementation is rare, a range of symptoms can occur, most of which result from hypercalcemia. We report a novel case of posterior reversible encephalopathy syndrome (PRES) in a young child who required intensive care after presenting with hypercalcemia, hypertensive emergency, acute kidney injury, and hypercarbic respiratory failure, which ultimately were attributed to vitamin D toxicity (VDT). We report a young child who developed PRES in association with VDT. Our report informs pediatric outpatient, hospitalist, and intensivist providers about rare but life-threatening complications from hypervitaminosis D, adds VDT to the differential diagnosis for children with similar presentations, and highlights the importance of vitamin supplementation safety guidance for families.
ABSTRACT
Age-related macular degeneration (AMD) is a debilitating eye disease that tends to affect people over the age of 55. Lipofuscins are autofluorescent, toxic byproducts of the visual cycle thought to contribute toward the progression of the disease. Targeting the accumulation of lipofuscin through catabolism may serve as a method for the early treatment of AMD. Thus, an enzymatic approach capable of degrading lipofuscin, cycloretinal (all-trans retinal dimer), was examined. A peroxidase from the organism Marasmius scorodonius (MsP1) has shown capability of degrading this toxic metabolite into nontoxic byproducts. A catalytic triad within MsP1 (D228, H365, and R388) was identified through multiple-sequence alignment and homology modeling and confirmed by kinetic analysis. MsP1-associated cleavage products were detected by gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and liquid chromatography-tandem mass spectrometry (LC-MSMS). MsP1 degradation byproducts of cycloretinal show reduced cytotoxicity within cell culture (ARPE-19), demonstrating its potential as a gene therapeutic to alleviate the buildup of lipofuscin within AMD.