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Glycogen storage disorder due to hepatic glycogen synthase deficiency(GSD0A)

MedGen UID:
343430
Concept ID:
C1855861
Disease or Syndrome
Synonyms: Glycogen storage disease due to hepatic glycogen synthase deficiency; Glycogen Storage Disease Type 0, Liver; GSD 0a; Hypoglycemia with deficiency of glycogen synthetase in the liver; LIVER GLYCOGEN SYNTHASE DEFICIENCY
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): GYS2 (12p12.1)
 
Monarch Initiative: MONDO:0009414
OMIM®: 240600
Orphanet: ORPHA2089

Definition

Glycogen storage disease type 0 (also known as GSD 0) is a condition caused by the body's inability to form a complex sugar called glycogen, which is a major source of stored energy in the body. GSD 0 has two types: in muscle GSD 0, glycogen formation in the muscles is impaired, and in liver GSD 0, glycogen formation in the liver is impaired.

The signs and symptoms of muscle GSD 0 typically begin in early childhood. Affected individuals often experience muscle pain and weakness or episodes of fainting (syncope) following moderate physical activity, such as walking up stairs. The loss of consciousness that occurs with fainting typically lasts up to several hours. Some individuals with muscle GSD 0 have a disruption of the heart's normal rhythm (arrhythmia) known as long QT syndrome. In all affected individuals, muscle GSD 0 impairs the heart's ability to effectively pump blood and increases the risk of cardiac arrest and sudden death, particularly after physical activity. Sudden death from cardiac arrest can occur in childhood or adolescence in people with muscle GSD 0.

Individuals with liver GSD 0 usually show signs and symptoms of the disorder in infancy. People with this disorder develop low blood sugar (glucose), known as hypoglycemia, after going long periods of time without food (fasting). Signs of hypoglycemia become apparent when affected infants begin sleeping through the night and stop late-night feedings; these infants exhibit extreme tiredness (lethargy), pale skin (pallor), and nausea. During episodes of fasting, ketone levels in the blood may increase (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars (such as glycogen) are unavailable. These short-term signs and symptoms of liver GSD 0 often improve when food is eaten and glucose levels in the body return to normal. The features of liver GSD 0 vary; they can be mild and go unnoticed for years, or they can include developmental delay and growth failure. [from MedlinePlus Genetics]

Clinical features

From HPO
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Ketosis
MedGen UID:
7206
Concept ID:
C0022638
Disease or Syndrome
Presence of elevated levels of ketone bodies in the body.
Neonatal hypoglycemia
MedGen UID:
57646
Concept ID:
C0158986
Finding
Blood glucose concentration below the lower limit of established reference ranges in a newborn.
Fasting hypoglycemia
MedGen UID:
75765
Concept ID:
C0271708
Disease or Syndrome
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Postprandial hyperglycemia
MedGen UID:
383702
Concept ID:
C1855520
Finding
An increased concentration of glucose in the blood following a meal.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGlycogen storage disorder due to hepatic glycogen synthase deficiency
Follow this link to review classifications for Glycogen storage disorder due to hepatic glycogen synthase deficiency in Orphanet.

Recent clinical studies

Etiology

Heller S, Worona L, Consuelo A
J Pediatr Gastroenterol Nutr 2008 Aug;47 Suppl 1:S15-21. doi: 10.1097/MPG.0b013e3181818ea5. PMID: 18667910
Wolfsdorf JI, Holm IA, Weinstein DA
Endocrinol Metab Clin North Am 1999 Dec;28(4):801-23. doi: 10.1016/s0889-8529(05)70103-1. PMID: 10609121

Diagnosis

Kasapkara ÇS, Aycan Z, Açoğlu E, Senel S, Oguz MM, Ceylaner S
J Pediatr Endocrinol Metab 2017 Apr 1;30(4):459-462. doi: 10.1515/jpem-2016-0317. PMID: 28245189
Weinstein DA, Correia CE, Saunders AC, Wolfsdorf JI
Mol Genet Metab 2006 Apr;87(4):284-8. Epub 2005 Dec 6 doi: 10.1016/j.ymgme.2005.10.006. PMID: 16337419Free PMC Article
Wolfsdorf JI, Holm IA, Weinstein DA
Endocrinol Metab Clin North Am 1999 Dec;28(4):801-23. doi: 10.1016/s0889-8529(05)70103-1. PMID: 10609121
Badizadegan K, Perez-Atayde AR
Hepatology 1997 Aug;26(2):365-73. doi: 10.1002/hep.510260217. PMID: 9252147
Arch Dis Child 1973 Feb;48(2):164-5. PMID: 4632229Free PMC Article

Therapy

Taylor KM, Meyers E, Phipps M, Kishnani PS, Cheng SH, Scheule RK, Moreland RJ
PLoS One 2013;8(2):e56181. Epub 2013 Feb 14 doi: 10.1371/journal.pone.0056181. PMID: 23457523Free PMC Article
Heller S, Worona L, Consuelo A
J Pediatr Gastroenterol Nutr 2008 Aug;47 Suppl 1:S15-21. doi: 10.1097/MPG.0b013e3181818ea5. PMID: 18667910
Gitzelmann R, Spycher MA, Feil G, Müller J, Seilnacht B, Stahl M, Bosshard NU
Eur J Pediatr 1996 Jul;155(7):561-7. doi: 10.1007/BF01957905. PMID: 8831078

Prognosis

Kasapkara ÇS, Aycan Z, Açoğlu E, Senel S, Oguz MM, Ceylaner S
J Pediatr Endocrinol Metab 2017 Apr 1;30(4):459-462. doi: 10.1515/jpem-2016-0317. PMID: 28245189
Taylor KM, Meyers E, Phipps M, Kishnani PS, Cheng SH, Scheule RK, Moreland RJ
PLoS One 2013;8(2):e56181. Epub 2013 Feb 14 doi: 10.1371/journal.pone.0056181. PMID: 23457523Free PMC Article
Lamperti C, Salani S, Lucchiari S, Bordoni A, Ripolone M, Fagiolari G, Fruguglietti ME, Crugnola V, Colombo C, Cappellini A, Prelle A, Bresolin N, Comi GP, Moggio M
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S161-8. Epub 2009 Apr 8 doi: 10.1007/s10545-009-1134-8. PMID: 19357989
Wolfsdorf JI, Holm IA, Weinstein DA
Endocrinol Metab Clin North Am 1999 Dec;28(4):801-23. doi: 10.1016/s0889-8529(05)70103-1. PMID: 10609121

Clinical prediction guides

Kasapkara ÇS, Aycan Z, Açoğlu E, Senel S, Oguz MM, Ceylaner S
J Pediatr Endocrinol Metab 2017 Apr 1;30(4):459-462. doi: 10.1515/jpem-2016-0317. PMID: 28245189
Taylor KM, Meyers E, Phipps M, Kishnani PS, Cheng SH, Scheule RK, Moreland RJ
PLoS One 2013;8(2):e56181. Epub 2013 Feb 14 doi: 10.1371/journal.pone.0056181. PMID: 23457523Free PMC Article
Hubner RH, Leopold PL, Kiuru M, De BP, Krause A, Crystal RG
Am J Respir Cell Mol Biol 2009 Feb;40(2):239-47. Epub 2008 Aug 7 doi: 10.1165/rcmb.2008-0029OC. PMID: 18688041Free PMC Article
Orho M, Bosshard NU, Buist NR, Gitzelmann R, Aynsley-Green A, Blümel P, Gannon MC, Nuttall FQ, Groop LC
J Clin Invest 1998 Aug 1;102(3):507-15. doi: 10.1172/JCI2890. PMID: 9691087Free PMC Article
Gitzelmann R, Spycher MA, Feil G, Müller J, Seilnacht B, Stahl M, Bosshard NU
Eur J Pediatr 1996 Jul;155(7):561-7. doi: 10.1007/BF01957905. PMID: 8831078

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