Natural Progression of Canine Glycogen Storage Disease Type IIIa

摘要

GlycogenstoragediseasetypeIIIa(GSDIIIa)iscausedbyadeficiencyofglycogendebranchingenzymeactivity.Hepatomegaly,muscledegeneration,andhypoglycemiaoccurinhumanpatientsatanearlyage.Long-termcomplicationsincludelivercirrhosis,hepaticadenomas,andgeneralizedmyopathy.AnaturallyoccurringcaninemodelofGSDIIIathatmimicsthehumandiseasehasbeendescribed,withprogressiveliverdiseaseandskeletalmuscledamagelikelyduetoexcessglycogendeposition.Inthecurrentstudy,long-termfollow-upofpreviouslydescribedGSDIIIadogsuntil32moofage(n=4)andoffamily-ownedGSDIIIadogsuntil11to12yofage(n=2)revealedthatelevatedconcentrationsofliverandmuscleenzyme(AST,ALT,ALP,andcreatinephosphokinase)decreasedovertime,consistentwithhepaticcirrhosisandmusclefibrosis.Glycogendepositioninmanyskeletalmuscles;thetongue,diaphragm,andheart;andthephrenicandsciaticnervesoccurredalso.Furthermore,theurinarybiomarkerGlcsub4/sub,whichhasbeendescribedinmanytypesofGSD,wasfirstelevatedandthendecreasedlaterinlife.ThisurinarybiomarkerdemonstratedasimilartrendasASTandALTinGSDIIIadogs,indicatingthatGlcsub4/submightbealessinvasivebiomarkerofhepatocellulardisease.Finally,thecurrentstudyfurtherdemonstratesthatthecanineGSDIIIamodeladherestotheclinicalcourseinhumanpatientswiththisdisorderandisanappropriatemodelfordevelopingnoveltherapies.