Type Ia Glycogen Storage Disease Workup

  • Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: George T Griffing, MD  more...
Updated: Apr 25, 2014

Laboratory Studies

See the list below:

  • Obtain a creatine kinase level in all cases of suspected glycogen storage disease (GSD).
  • Because hypoglycemia may be found in some types of GSD, fasting glucose testing is indicated. Hypoglycemia is concerning and may lead to hypoglycemic seizures.
  • Urine studies are indicated because myoglobinuria may occur in some GSDs.
  • Hepatic failure occurs in some GSDs. Liver function studies are indicated.
  • Hyperlipidemia is found in GSD Ia although there is no clear evidence of increased atherosclerosis.[6]
  • Laboratory abnormalities also include hyperuricemia, hyperlactacidemia, hyperlipidemia, hypercalciuria, and azotemia.
  • Normochromic anemia has been documented.
  • Measuring lipase and amylase may be justified in suspected cases of pancreatitis.
  • Renal function studies may reveal renal failure. Nephropathy is a serious long-term complication of von Gierke disease.
  • Obtaining a 24-hour urine collection to measure protein and creatinine clearance may be useful.
  • Nutritional status
    • Kishnani and colleagues reported on 1 patient with von Gierke disease who was compliant with a high-protein diet but who developed emesis, weight loss, weakness, ataxia, agraphia, and oral ulcers. He was found to be deficient in vitamin B-12, folate, and iron. Correction of deficiencies allowed for symptomatic recovery.[7]
    • Other authors note that oral ulcers are secondary to impaired neutrophil migration, one feature of this disorder.

Imaging Studies

See the list below:

  • Imaging may reveal hepatic adenoma, which may become malignant.
  • Bone densitometry in older individuals may show low bone mass.
  • Renal ultrasonography may show enlarged kidneys.
  • In a study to determine how well contrast-enhanced ultrasonographic scans can characterize focal liver lesions in patients with GSD type Ia, Nguyen et al examined images from 8 benign hepatic adenomas associated with the disease.[8] The scans revealed marked hypervascularity in all of the lesions during the early arterial phase, with most of the lesions showing sustained enhancement in the portal and late phases.

Other Tests

See the list below:

  • Ischemic forearm test
    • The ischemic forearm test is an important tool for diagnosis of muscle disorders. The basic premise is an analysis of the normal chemical reactions and products of muscle activity. Obtain consent before the test.
    • Instruct the patient to rest. Position a loosened blood pressure cuff on the arm, and place a venous line for blood samples from the antecubital vein.
    • Obtain blood samples for the following tests: creatine kinase, ammonia, and lactate. Repeat in 5-10 minutes.
    • Obtain a urine sample for myoglobin analysis.
    • Immediately inflate the blood pressure cuff above systolic blood pressure and have the patient repetitively grasp an object, such as a dynamometer. Instruct the patient to grasp the object firmly, once or twice per second. Encourage the patient for 2-3 minutes, at which time the patient may no longer be able to participate. Immediately release and remove the blood pressure cuff.
    • Obtain blood samples for creatine kinase, ammonia, and lactate immediately and at 5, 10, and 20 minutes.
    • Collect a final urine sample for myoglobin analysis.
  • Interpretation of ischemic forearm test results
    • With exercise, carbohydrate metabolic pathways yield lactate from pyruvate. Lack of lactate production during exercise is evidence of a pathway disturbance, and an enzyme deficiency is suggested. In such cases, muscle biopsy with biochemical assay is indicated.
    • Healthy patients demonstrate an increase in lactate of at least 5-10 mg/dL and ammonia of at least 100 mcg/dL. Levels will return to baseline.
    • If neither level increases, the exercise was not strenuous enough and the test is not valid.
    • Increased lactate at rest (before exercise) is evidence of mitochondrial myopathy.
    • Failure of lactate to increase with ammonia is evidence of a GSD resulting in a block in carbohydrate metabolic pathways. Not all patients with GSDs have a positive ischemic test.
    • Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
    • In von Gierke disease, the ischemic forearm test is negative.
  • Molecular genetic analysis
    • Seydewitz and Matern report a study of 40 patients with von Gierke disease. Mutations were found on all 80 alleles, which is evidence that molecular genetic analysis is a reliable diagnostic modality in addition to enzyme assay.[9]
    • Biochemical assay of enzyme activity is required for definitive diagnosis.

Histologic Findings

Biopsy of the kidney reveals focal glomerulosclerosis.

Contributor Information and Disclosures

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: California Medical Association, American Headache Society, San Francisco Medical Society, San Francisco Medical Society, International Headache Society, California Neurology Society, San Francisco Neurological Society, American Academy of Neurology, California Medical Association

Disclosure: Received honoraria from Teva for speaking and teaching; Received grant/research funds from Allergan for other; Received honoraria from Insys for speaking and teaching; Received honoraria from DepoMed for speaking and teaching.

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 the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

  1. 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. [Medline].

  2. 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. [Medline].

  3. Bandsma RH, Prinsen BH, van Der Velden Mde S, et al. Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to hyperlipidemia in glycogen storage disease type 1a. Pediatr Res. 2008 Jun. 63(6):702-7. [Medline].

  4. 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. [Medline]. [Full Text].

  5. 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. [Medline].

  6. 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. [Medline].

  7. Kishnani PS, Boney A, Chen YT. Nutritional deficiencies in a patient with glycogen storage disease type Ib. J Inherit Metab Dis. 1999 Oct. 22(7):795-801. [Medline].

  8. 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. [Medline].

  9. 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. [Medline].

  10. 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. [Medline].

  11. 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. [Medline].

  12. 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. [Medline].

  13. Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. 2000 Feb. 18(1):151-65. [Medline].

  14. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan. 105(1):e10. [Medline].

  15. 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.

  16. 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.

  17. 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. [Medline].

  18. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc. 1993 Dec. 93(12):1423-30. [Medline].

  19. Hou DC, Kure S, Suzuki Y. Glycogen storage disease type Ib: structural and mutational analysis of the microsomal glucose-6-phosphate transporter gene. Am J Med Genet. 1999 Sep 17. 86(3):253-7. [Medline].

  20. Lin B, Hiraiwa H, Pan CJ. Type-1c glycogen storage disease is not caused by mutations in the glucose-6-phosphate transporter gene. Hum Genet. 1999 Nov. 105(5):515-7. [Medline].

  21. Moses SW. Historical highlights and unsolved problems in glycogen storage disease type 1. Eur J Pediatr. 2002 Oct. 161 Suppl 1:S2-9. [Medline].

  22. Orho M, Bosshard NU, Buist NR. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. J Clin Invest. 1998 Aug 1. 102(3):507-15. [Medline].

  23. Pears JS, Jung RT, Hopwood D. Glycogen storage disease diagnosed in adults. Q J Med. 1992 Mar. 82(299):207-22. [Medline].

  24. Reitsma-Bierens WC. Renal complications in glycogen storage disease type I. Eur J Pediatr. 1993. 152 Suppl 1:S60-2. [Medline].

  25. Salapata Y, Laskaris G, Drogari E. Oral manifestations in glycogen storage disease type 1b. J Oral Pathol Med. 1995 Mar. 24(3):136-9. [Medline].

  26. Smit GP, Fernandes J, Leonard JV. The long-term outcome of patients with glycogen storage diseases. J Inherit Metab Dis. 1990. 13(4):411-8. [Medline].

  27. Stevens AN, Iles RA, Morris PG. Detection of glycogen in a glycogen storage disease by 13C nuclear magnetic resonance. FEBS Lett. 1982 Dec 27. 150(2):489-93. [Medline].

  28. Veiga-da-Cunha M, Gerin I, Chen YT. The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. Eur J Hum Genet. 1999 Sep. 7(6):717-23. [Medline].

  29. Wolfsdorf JI, Holm IA, Weinstein DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am. 1999 Dec. 28(4):801-23. [Medline].

  30. Yang Chou J, Mansfield BC. Molecular Genetics of Type 1 Glycogen Storage Diseases. Trends Endocrinol Metab. 1999 Apr. 10(3):104-113. [Medline].

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