RT Book, Section
A1 Weinstein, David A.
A1 Wolfsdorf, Joseph I.
A1 Smit, Peter A.
A1 Schoser, Benedikt
A2 Sarafoglou, Kyriakie
A2 Hoffmann, Georg F.
A2 Roth, Karl S.
SR Print(0)
ID 1140314887
T1 Glycogen Storage Diseases
T2 Pediatric Endocrinology and Inborn Errors of Metabolism, 2e
YR 2017
FD 2017
PB McGraw-Hill Education
PP New York, NY
SN 9780071773140
LK accesspediatrics.mhmedical.com/content.aspx?aid=1140314887
RD 2024/04/19
AB The  glycogen  storage  diseases  (GSD)  comprise  several  inherited  diseases  caused  by  abnormalities  of  the  enzymes  that  regulate  glycogen  synthesis  and  degradation.1,2  Glycogen  is  stored  principally  in  liver  and  muscle.  Muscle  lacks  glucose-6-phosphatase  (G6Pase)  and  therefore  is  unable  to  release  glucose  for  systemic  use.  Hypoglycemia  is  the  primary  manifestation  of  the  hepatic  glycogenoses,  whereas  weakness  and  muscle  cramps  are  the  predominant  features  of  the  muscle  glycogenoses.  After  a  meal,  glucose  is  stored  as  glycogen,  a  complex,  insoluble,  highly  branched  polymer  that  allows  efficient  storage  and  release  of  glucose.  The  liver  is  freely  permeable  to  glucose,  which  is  rapidly  phosphorylated  by  glucokinase  to  form  glucose-6-phosphate.  Glucose-6-phosphate  is  subsequently  converted  to  glucose-1-phosphate,  the  starting  point  for  glycogen  synthesis.  Glycogen  synthase  creates  chains  of  glucose  molecules  by  catalyzing  the  formation  of  α-1,4-linkages.  A  branching  enzyme  forms  α-1,6-linkages  approximately  every  10  glucose  units  along  the  chain.  In  between  meals,  glycogen  is  degraded  by  the  sequential  action  of  two  enzymes:  hepatic  glycogen  phosphorylase  and  debranching  enzyme.  Debranching  enzyme  has  two  enzymatic  activities:  transferase  and  amylo-1,6-glucosidase  activity.  Glycogen  phosphorylase  is  the  rate-limiting  enzyme  in  glycogenolysis,  which  hydrolyzes  the  α-1,4-linkages  from  the  outer  branches  of  glycogen  until  only  four  glucosyl  units  remain  distal  to  the  α-1,6  branch  point.  Then  the  debranching  enzyme  through  its  transferase  activity  transfers  three  of  the  glucosyl  residues  to  the  outer  end  of  an  adjacent  chain  and  through  its  amylo-1,6-glucosidase  activity  hydrolyses  the  branch  point  glucose  residue  (Figure  5-1).  The  main  physiological  functions  of  glycogen  in  skeletal  muscle  is  providing  substrate  for  glycolysis.  At  the  start  of  exercise  and  during  high-intensity  exercise,  the  muscle  depends  solely  on  muscle  glycogen  breakdown.  Intact  metabolic  pathways  in  glycogen  and  glucose  breakdown  are  consequently  essential  for  preserving  aerobic  power  to  fuel  muscles  on  the  move.  There  are  two  central  forms  of  clinical  presentation  of  muscular  glycogen  storage  diseases,  those  with  static  muscle  wasting  and  weakness,  and  those  with  dynamic,  exercise-induced  symptoms.  Sometimes  both  presentations  may  overlap.