Type VI Glycogen Storage Disease Workup
- Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: George T Griffing, MD more...
Lab studies include the following:
- Obtain a creatine kinase level in all cases of suspected glycogen storage disease (GSD).
- Urine studies are indicated because myoglobinuria may occur in some patients with GSDs.
- Hepatic failure occurs in some patients with GSDs, although rarely in those with Hers disease. Liver function studies are indicated and may reveal evidence of hepatic injury.
- Biochemical assay of enzyme activity is necessary for definitive diagnosis.
- Manzia et al reported the first documented case of GSD associated with a rapidly growing hepatocellular adenoma as determined by histological findings.
Findings from imaging studies may reveal hepatomegaly.
Ischemic forearm test
- In the case of Hers disease, which is not associated with significant muscle involvement, the forearm ischemic test is most useful to help rule out other GSDs, most specifically Cori disease, McArdle disease, and Tarui disease. Test findings are expected to be negative in patients with Hers disease.
- 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 in 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 positive ischemic test results.
- Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
- Positive ischemic forearm test results may occur in patients with Cori disease, McArdle disease, and Tarui disease.
- In patients with Hers disease, ischemic test results are negative.
Liver biopsy may be required to diagnose the cause of hepatomegaly.
Brown LM, Corrado MM, van der Ende RM, Derks TG, Chen MA, Siegel S, et al. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children. J Inherit Metab Dis. 2014 Jul 29. [Medline].
Parker EI, Xing M, Moreno-De-Luca A, Harmouche E, Terk MR. Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders. Br J Radiol. 2014 Jan. 87(1033):20130467. [Medline]. [Full Text].
Manzia TM, Angelico R, Toti L, Cillis A, Ciano P, Orlando G, et al. Glycogen storage disease type Ia and VI associated with hepatocellular carcinoma: two case reports. Transplant Proc. 2011 May. 43(4):1181-3. [Medline].
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].
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].
Asami T, Kikuchi T, Asami K. Effect of clonidine on the height of a child with glycogen storage disease type VI: a 13 year follow-up study. Acta Paediatr Jpn. 1996 Oct. 38(5):524-8. [Medline].
Ji HF, Wang WL, Shen Y, et al. Reduced-size liver transplantation for glycogen storage disease. Hepatobiliary Pancreat Dis Int. 2009 Feb. 8(1):106-8. [Medline].
Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. 2000 Feb. 18(1):151-65. [Medline].
Aminoff MJ, ed. Electromyography in Clinical Practice. 3rd ed. New York, NY: Churchill Livingstone; 1998.
Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan. 105(1):e10. [Medline].
Burwinkel B, Bakker HD, Herschkovitz E. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet. 1998 Apr. 62(4):785-91. [Medline].
Chen Y. Glycogen Storage Diseases. Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2000. Vol 1: 1537-8.
DiMauro S, Bruno C. Glycogen storage diseases of muscle. Curr Opin Neurol. 1998 Oct. 11(5):477-84. [Medline].
Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc. 1993 Dec. 93(12):1423-30. [Medline].
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].
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].
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].
Tang NL, Hui J, Young E, et al. A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity. Mol Genet Metab. 2003 Jun. 79(2):142-5. [Medline].
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].