Persistent acidosis and chronic kidney disease in a patient with type 1 glycogen storage disease.

Type 1 glycogen storage disease (GSDI) is a rare autosomal recessive disorder caused by glucose-6-phosphatase (G6Pase) deficiency. We discuss a case of a 29-year-old gentleman who had GSDI with metabolic complications of hypoglycemia, hypertriglyceridemia, hyperuricemia, and short stature. He also suffered from advanced chronic kidney disease, nephrotic range proteinuria, and hepatic adenomas. He presented with acute pneumonia and refractory metabolic acidosis despite treatment with isotonic bicarbonate infusion, reversal of hypoglycemia, and lactic acidosis. He eventually required kidney replacement therapy. The case report highlights the multiple contributing mechanisms and challenges to managing refractory metabolic acidosis in a patient with GSDI. Important considerations for dialysis initiation, decision for long-term dialysis modality and kidney transplantation for patients with GSDI are also discussed in this case report.

The adenylate cyclase UvAc1 and phosphodiesterase UvPdeH control the intracellular cAMP level, development, and pathogenicity of the rice false smut fungus Ustilaginoidea virens.

The cyclic adenosine monophosphate (cAMP) signaling pathway plays pleiotropic roles in regulating development and pathogenicity in eukaryotes. cAMP is a second messenger that is important for the activation of downstream pathways. The intracellular cAMP level is modulated mainly by its biosynthesis, which is catalyzed by adenylate cyclases (ACs), and hydrolysis by phosphodiesterases (PDEs). Here, we identified the AC UvAc1 and the cAMP high-affinity PDE UvPdeH in the rice false smut fungus Ustilaginoidea virens; these enzymes are homologs of MoMac1 and MoPdeH in Magnaporthe oryzae (rice blast fungus). A heterogenous complementation assay revealed that UvAc1 and UvPdeH partially or completely rescued the defects in ΔMomac1 and ΔMopdeH mutant M. oryzae. UvAc1 and UvPdeH play important roles in the development and virulence of U. virens. ΔUvac1 and ΔUvpdeH mutant fungi showed defects in conidial production, morphology, and germination; reduced toxicity against germinating rice seeds; and reduced virulence on rice panicles. ΔUvac1 exhibited increased sensitivity to Calcofluor White (CFW) and sodium chloride (NaCl), and decreased sensitivity to Congo Red (CR), while ΔUvpdeH showed increased sensitivity to sodium dodecyl sulfate, CR, sorbitol, and hydrogen peroxide, and decreased sensitivity to CFW and NaCl. High-performance liquid chromatography revealed that the intracellular cAMP level was significantly increased in ΔUvpdeH and decreased in ΔUvac1. Taken together, our results demonstrate that UvAc1 and UvPdeH are conservative components of the cAMP pathway that are important for conidiogenesis, stress responses, virulence, and regulation of the intracellular cAMP level in U. virens.

Salicylic acid stimulates secretion of the normally symplastic enzyme mannitol dehydrogenase: a possible defense against mannitol-secreting fungal pathogens.

The sugar alcohol mannitol is an important carbohydrate with well-documented roles in both metabolism and osmoprotection in many plants and fungi. In addition to these traditionally recognized roles, mannitol is reported to be an antioxidant and as such may play a role in host-pathogen interactions. Current research suggests that pathogenic fungi can secrete mannitol into the apoplast to suppress reactive oxygen-mediated host defenses. Immunoelectron microscopy, immunoblot, and biochemical data reported here show that the normally symplastic plant enzyme, mannitol dehydrogenase (MTD), is secreted into the apoplast after treatment with the endogenous inducer of plant defense responses salicylic acid (SA). In contrast, a cytoplasmic marker protein, hexokinase, remained cytoplasmic after SA-treatment. Secreted MTD retained activity after export to the apoplast. Given that MTD converts mannitol to the sugar mannose, MTD secretion may be an important component of plant defense against mannitol-secreting fungal pathogens such as Alternaria. After SA treatment, MTD was not detected in the Golgi apparatus, and its SA-induced secretion was resistant to brefeldin A, an inhibitor of Golgi-mediated protein transport. Together with the absence of a known extracellular targeting sequence on the MTD protein, these data suggest that a plant's response to pathogen challenge may include secretion of selected defensive proteins by as yet uncharacterized, non-Golgi mechanisms.