Oral manifestations of primary hyperoxaluria in adult patient

Primary hyperoxaluria (PH) is a rare disease, autosomal recessive inheritance disorder. This disease leads to overproduction of oxalates, and the excretation inability results in deposition of calcium oxalate crystals in almost all tissues presenting the oxalosis condition. The treatment is a combined liver and kidney transplantation (CLKT), which enables a better patient survival. Due to this survival, the patients had could present a several oral manifestations such as periodontal disease, root resorption, dental pain and increased tooth mobility. However, currently, there is a lack of information in the literature about all oral manifestations that this patient can present. Beside this, there are doubt and challenge about treatments to this patient in these different oral manifestations. The present study aims to report a case of a patient with hyperoxaluria type I with oxalosis oral manifestations.

Dimerization Drives Proper Folding of Human Alanine:Glyoxylate Aminotransferase But Is Dispensable for Peroxisomal Targeting

Peroxisomal matrix proteins are transported into peroxisomes in a fully-folded state, but whether multimeric proteins are imported as monomers or oligomers is still disputed. Here, we used alanine:glyoxylate aminotransferase (AGT), a homodimeric pyridoxal 5′-phosphate (PLP)-dependent enzyme, whose deficit causes primary hyperoxaluria type I (PH1), as a model protein and compared the intracellular behavior and peroxisomal import of native dimeric and artificial monomeric forms. Monomerization strongly reduces AGT intracellular stability and increases its aggregation/degradation propensity. In addition, monomers are partly retained in the cytosol. To assess possible differences in import kinetics, we engineered AGT to allow binding of a membrane-permeable dye and followed its intracellular trafficking without interfering with its biochemical properties. By fluorescence recovery after photobleaching, we measured the import rate in live cells. Dimeric and monomeric AGT displayed a similar import rate, suggesting that the oligomeric state per se does not influence import kinetics. However, when dimerization is compromised, monomers are prone to misfolding events that can prevent peroxisomal import, a finding crucial to predicting the consequences of PH1-causing mutations that destabilize the dimer. Treatment with pyridoxine of cells expressing monomeric AGT promotes dimerization and folding, thus, demonstrating the chaperone role of PLP. Our data support a model in which dimerization represents a potential key checkpoint in the cytosol at the crossroad between misfolding and correct targeting, a possible general mechanism for other oligomeric peroxisomal proteins.