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Glycogen Storage Disease, Type Ib: Differential Diagnoses & Workup

Author: Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Contributor Information and Disclosures

Updated: Sep 20, 2007

Differential Diagnoses

Glucose-6-Phosphatase Deficiency
Glycogen Storage Disease, Type VI
Glucose-6-Phosphate Dehydrogenase Deficiency
Glycogen Storage Disease, Type VII
Glycogen Storage Disease, Type Ia
Hepatic Carcinoma, Primary
Glycogen Storage Disease, Type II
Hepatic Cysts
Glycogen Storage Disease, Type III
Hepatic Failure
Glycogen Storage Disease, Type IV
Hypoglycemia
Glycogen Storage Disease, Type V

Workup

Laboratory Studies

  • Obtain a creatine kinase in all cases of suspected glycogen storage disease (GSD).
  • Obtain a lipid profile due to changes in glucose metabolism.
  • Because hypoglycemia may be found in some types of GSD, fasting glucose 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.
  • Biochemical assay is required for definitive diagnosis.

Imaging Studies

  • Imaging may reveal hepatic adenoma, which may become malignant.

Other Tests

  • 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 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 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 µg/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 GSDs have a positive ischemic test.
    • Failure of ammonia to increase with lactate is evidence of myoadenylate deaminase deficiency.
    • Ischemic forearm test is normal in GSD type Ib.
  • Electromyelography
    • Aminoff reports electromyelographic findings suggestive of myopathy, although abnormal spontaneous activity may be present.
    • Electrical myotonia without clinical myotonia may be present.
    • Myotonic discharges may be found in the paraspinal muscles.
    • Fibrillation potentials, positive sharp waves, and complex repetitive discharges may be found.
    • Myopathic findings of polyphasic responses, decreased duration of potentials, and decreased amplitude usually are present.
  • ECG demonstrates a pan-lead, short PR interval and elevated QRS complexes in the infantile form.

Procedures

Given the association of inflammatory bowel disease, endoscopic procedures may be necessary.

Histologic Findings

Liver histology is characterized by hepatocytes distended by glycogen and fat. Associated fibrosis is minimal.

More on Glycogen Storage Disease, Type Ib

Overview: Glycogen Storage Disease, Type Ib
Differential Diagnoses & Workup: Glycogen Storage Disease, Type Ib
Treatment & Medication: Glycogen Storage Disease, Type Ib
Follow-up: Glycogen Storage Disease, Type Ib
Multimedia: Glycogen Storage Disease, Type Ib
References
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References

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  2. D'Eufemia P, Finocchiaro R, Celli M, Zambrano A, Tetti M, Ferrucci V. Absence of severe recurrent infections in glycogen storage disease type Ib with neutropenia and neutrophil dysfunction. J Inherit Metab Dis. Feb 2007;30(1):105. [Medline].

  3. 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. Sep 2002;141(3):350-6. [Medline].

  4. Zingone A, Hiraiwa H, Pan CJ. Correction of glycogen storage disease type 1a in a mouse model by gene therapy. J Biol Chem. Jan 14 2000;275(2):828-32. [Medline].

  5. Bijvoet AG, Van Hirtum H, Vermey M. Pathological features of glycogen storage disease type II highlighted in the knockout mouse model. J Pathol. Nov 1999;189(3):416-24. [Medline].

  6. Matern D, Starzl TE, Arnaout W. Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr. Dec 1999;158 Suppl 2:S43-8. [Medline].

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Further Reading

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Keywords

GSD type Ib, GSD type 1b, glycogen storage disorder, GSD, glycogen storage disease, Pompe disease, GSD type II, acid maltase deficiency, Cori disease, GSD type III, debranching enzyme deficiency, McArdle disease, GSD type V, myophosphorylase deficiency, Tarui disease, GSD type VII, phosphofructokinase deficiency, von Gierke disease, GSD type Ia, glucose-6-phosphatase deficiency, glucose-6-phosphatase, G-6-P, hypoglycemic seizure

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Contributor Information and Disclosures

Author

Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Wayne E Anderson, DO is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Medical Association, American Society of Law Medicine and Ethics, California Medical Association, and San Francisco Medical Society
Disclosure: Cephalon Honoraria Speaking and teaching; Janssen Honoraria Speaking and teaching; Ligand Honoraria Consulting; Alpharma Honoraria Speaking and teaching

Medical Editor

Barry J Goldstein, MD, PhD, Director, Division of Endocrinology, Diabetes and Metabolic Diseases, Professor, Department of Internal Medicine, Thomas Jefferson University
Barry J Goldstein, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MD, Head, Vascular Division, Baker Medical Research Institute; Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, Director of General Internal Medicine, St Louis University
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

 
 
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