History

The initial presentation is most often characterized by abdominal distension and failure to thrive. Patients may present with hypoglycemic seizures or coma.^[9]

Global muscle weakness is not a typical feature of von Gierke disease. Schwahn et al found height, weight, bone mass, and grip force decreased in one group of GSD 1a patients.^[10] Older patients may give a history of kidney stones, gout, or pancreatitis.

Patients may have delayed puberty. Intellectual development may be diminished, especially in patients who have experienced coma.^[9]

A prospective study by Melis et al found that GSD Ia patients had a higher prevalence of insulin resistance and metabolic syndrome.^[11]

Physical Examination

Physical examination may reveal the following findings:

Hepatomegaly or abdominal distension
Tachypnea in infants as a respiratory mode of compensation for lactic acidosis
Characteristic round facies
Xanthomas on the buttocks or extensor surfaces
Acute manifestations of gout
Hypertension or other manifestations of renal failure
Short stature^[9]

Differential Diagnoses

Araoka T, Takeoka H, Abe H, Kishi S, Araki M, Nishioka K, et al. Early diagnosis and treatment may prevent the development of complications in an adult patient with glycogen storage disease type Ia. Intern Med. 2010. 49(16):1787-92. [QxMD MEDLINE Link].
Yang Chou J, Mansfield BC. Molecular genetics of type 1 glycogen storage diseases. Trends Endocrinol Metab. 1999 Apr. 10(3):104-13. [QxMD MEDLINE Link].
Van Schaftingen E, Gerin I. The glucose-6-phosphate system. Biochem J. 2002 Mar 15. 362:516-532. [QxMD MEDLINE Link]. [Full Text].
Ai J, He W, Huang X et al. A case report of acute pancreatitis with glycogen storage disease type IA in an adult patient and review of the literature. Medicine. 2020 Oct 16. 99:e22644. [QxMD MEDLINE Link]. [Full Text].
Derks T, van Rijn M. Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions. J Inherit Metab Dis. 2015 Jan 30. 38:537–543. [QxMD MEDLINE Link].
Wang DQ, Fiske LM, Carreras CT, Weinstein DA. Natural history of hepatocellular adenoma formation in glycogen storage disease type I. J Pediatr. 2011 Sep. 159(3):442-6. [QxMD MEDLINE Link]. [Full Text].
Reitsma-Bierens WC. Renal complications in glycogen storage disease type I. Eur J Pediatr. 1993. 152 Suppl 1:S60-2. [QxMD MEDLINE Link].
Ekstein J, Rubin BY, Anderson SL, Weinstein DA, Bach G, Abeliovich D, et al. Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population. Am J Med Genet A. 2004 Aug 30. 129A (2):162-4. [QxMD MEDLINE Link].
Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit GP. Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). Eur J Pediatr. 2002 Oct. 161 Suppl 1:S20-34. [QxMD MEDLINE Link].
Schwahn B, Rauch F, Wendel U, Schönau E. Low bone mass in glycogen storage disease type 1 is associated with reduced muscle force and poor metabolic control. J Pediatr. 2002 Sep. 141(3):350-6. [QxMD MEDLINE Link].
Melis D, Rossi A, Pivonello R, Salerno M, Balivo F, Spadarella S, et al. Glycogen storage disease type Ia (GSDIa) but not Glycogen storage disease type Ib (GSDIb) is associated to an increased risk of metabolic syndrome: possible role of microsomal glucose 6-phosphate accumulation. Orphanet J Rare Dis. 2015 Jul 29. 10:91. [QxMD MEDLINE Link].
Beyzaei Z, Geramizadeh B. Molecular diagnosis of glycogen storage disease type I: a review. EXCLI J. 2019. 18:30-46. [QxMD MEDLINE Link].
McAdams AJ, Hug G, Bove KE. Glycogen storage disease, types I to X: criteria for morphologic diagnosis. Hum Pathol. 1974 Jul. 5 (4):463-87. [QxMD MEDLINE Link].
Kalkan Ucar S, Coker M, et al. A monocentric pilot study of an antioxidative defense and hsCRP in pediatric patients with glycogen storage disease type IA and III. Nutr Metab Cardiovasc Dis. 2009 Jul. 19(6):383-90. [QxMD MEDLINE Link].
Rake JP, Visser G, Huismans D, Huitema S, van der Veer E, Piers DA, et al. Bone mineral density in children, adolescents and adults with glycogen storage disease type Ia: a cross-sectional and longitudinal study. J Inherit Metab Dis. 2003. 26 (4):371-84. [QxMD MEDLINE Link].
Nguyen AT, Bressenot A, Manole S, et al. Contrast-enhanced ultrasonography in patients with glycogen storage disease type Ia and adenomas. J Ultrasound Med. 2009 Apr. 28(4):497-505. [QxMD MEDLINE Link].
Zingone A, Hiraiwa H, Pan CJ. Correction of glycogen storage disease type 1a in a mouse model by gene therapy. J Biol Chem. 2000 Jan 14. 275(2):828-32. [QxMD MEDLINE Link].
Bijvoet AG, Van Hirtum H, Vermey M. Pathological features of glycogen storage disease type II highlighted in the knockout mouse model. J Pathol. 1999 Nov. 189(3):416-24. [QxMD MEDLINE Link].
Zhang L, Lee C, Arnaoutova I, Anduaga J, Starost MF, Mansfield BC, et al. Gene therapy using a novel G6PC-S298C variant enhances the long-term efficacy for treating glycogen storage disease type Ia. Biochem Biophys Res Commun. 2020 Jun 30. 527 (3):824-830. [QxMD MEDLINE Link].
Arnaoutova I, Zhang L, Chen HD, Mansfield BC, Chou JY. Correction of metabolic abnormalities in a mouse model of glycogen storage disease type Ia by CRISPR/Cas9-based gene editing. Mol Ther. 2021 Apr 7. 29 (4):1602-1610. [QxMD MEDLINE Link].
Matern D, Starzl TE, Arnaout W. Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr. 1999 Dec. 158 Suppl 2:S43-8. [QxMD MEDLINE Link].
Jones JG, Garcia P, Barosa C, et al. Hepatic anaplerotic outflow fluxes are redirected from gluconeogenesis to lactate synthesis in patients with Type 1a glycogen storage disease. Metab Eng. 2009 May. 11(3):155-62. [QxMD MEDLINE Link].
Seydewitz HH, Matern D. Molecular genetic analysis of 40 patients with glycogen storage disease type Ia: 100% mutation detection rate and 5 novel mutations. Hum Mutat (Online). 2000 Jan. 15(1):115-6. [QxMD MEDLINE Link].
Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. 2000 Feb. 18(1):151-65. [QxMD MEDLINE Link].
Chen Y. Glycogen Storage Diseases. Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Basis of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. 1521-51.
Fernandes J, Smit G. The Glycogen Storage Diseases. Fernandes J, Saudubray JM, Van Den Berghe G, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 3rd ed. New York, NY: Springer-Verlag; 2000. 87-101.
Geberhiwot T, Alger S, McKiernan P, Packard C, Caslake M, Elias E. Serum lipid and lipoprotein profile of patients with glycogen storage disease types I, III and IX. J Inherit Metab Dis. 2007 Jun. 30(3):406. [QxMD MEDLINE Link].
Moses SW. Historical highlights and unsolved problems in glycogen storage disease type 1. Eur J Pediatr. 2002 Oct. 161 Suppl 1:S2-9. [QxMD MEDLINE Link].

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Metabolic pathways of carbohydrates

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Author

Kathleen R Ruddiman, DO Fellow Physician, Department of Endocrinology, Atrium Health Wake Forest Baptist Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Catherine Anastasopoulou, MD, PhD, FACE Associate Professor of Medicine, The Steven, Daniel and Douglas Altman Chair of Endocrinology, Sidney Kimmel Medical College of Thomas Jefferson University; Einstein Endocrine Associates, Einstein Medical Center

Catherine Anastasopoulou, MD, PhD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Society for Bone and Mineral Research, Endocrine Society, Philadelphia Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kent Wehmeier, MD Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine

Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for Physician Leadership, American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society, International Society for Clinical Densitometry, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Wayne E Anderson, DO, FAHS, FAAN Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Wayne E Anderson, DO, FAHS, FAAN is a member of the following medical societies: American Academy of Neurology, American Headache Society, California Medical Association, California Neurology Society, International Headache Society, San Francisco Medical Society, San Francisco Neurological Society

Disclosure: Nothing to disclose.