Genetics of Glycogen-Storage Disease Type III Follow-up

  • Author: David H Tegay, DO, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 13, 2012
 

Further Inpatient Care

Any condition that precludes adequate oral or enteral intake of nutrients requires hospital admission to administer intravenous glucose.

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Further Outpatient Care

A physician experienced in glycogen-storage disease (GSD) type III (GSD III) management, preferably a biochemical geneticist, should provide follow-up care at least every 6 months. More frequent follow-up is recommended during the first year after diagnosis and during the patient's pubertal growth spurt.

Follow-up appointments should include a complete physical examination focused on the growth of the patient.

Periodically evaluate patients for liver function, appearance of hepatic adenomas, and muscle strength.[26]

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Inpatient & Outpatient Medications

See Medication.

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Transfer

Strongly consider transfer to a tertiary care center to treat any problems that cannot be promptly resolved by intravenous glucose administration to maintain adequate blood glucose levels.

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Deterrence/Prevention

Instruct parents and patients about dangers of fasting hypoglycemia and of fasting more than 5-7 hours. Parents and patients should pay special attention to periods of reduced oral intake that result from concurrent illness.

Advise patients to avoid strenuous activity at times when blood glucose levels are not within reference ranges. Failure to do so creates a remote danger of rhabdomyolysis, which may lead to myoglobinuria and acute renal failure.

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Complications

Complications include the following:

  • Profound hypoglycemia, cerebral edema, coma, and death
  • Cirrhosis and liver failure[7]
  • Hepatic adenoma and hepatocellular carcinoma[7]
  • Myopathy with progressive muscle weakness and distal muscle wasting
  • Hypertrophic cardiomyopathy
  • Acute renal failure secondary to rhabdomyolysis and myoglobinuria following strenuous activity at times when blood glucose levels are not within reference ranges
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Prognosis

Patients receiving proper management of their blood glucose levels should not encounter life-threatening hypoglycemia.

Some patients develop cirrhosis and even liver failure. Liver transplantation is an option.[28]

Cirrhosis may lead to hepatocellular carcinoma.

Some patients develop hypertrophic cardiomyopathy, yet overt cardiac dysfunction is rare.

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Patient Education

Teach all caregivers and sufficiently mature patients how to recognize signs of impending hypoglycemia.

Teach all caregivers and sufficiently mature patients how to manage hypoglycemic episodes.

Teach all caregivers and sufficiently mature patients how to measure blood glucose levels.

Teach all caregivers how to insert an nasogastric tube (NGT) and how to use an infusion pump.

Provide intensive nutritional education to caregivers and sufficiently mature patients.

Encourage sufficiently mature patients to participate in the dietary management of their disease.

The following organizations provide excellent information for families of patients with GSD III:

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Contributor Information and Disclosures
Author

David H Tegay, DO, FACMG  Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center

David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association, American Society of Human Genetics, and Federation of American Societies for Experimental Biology

Disclosure: Nothing to disclose.

Coauthor(s)

Riya Jose  Medicine Department Academic Fellow, New York College of Osteopathic Medicine of the New York Institute of Technology

Disclosure: Nothing to disclose.

Specialty Editor Board

Edward Kaye, MD  Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders

Disclosure: Genzyme Corporation Salary Management position

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Howard R Sloan, MD, PhD to the development and writing of this article.

References

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Schematic illustration of the degradation of glycogen by the concerted action of the enzymes phosphorylase and debranching enzyme. First, phosphorylase removes glucose moieties (linked to their neighbors via alpha1,4 glucosidic bonds and depicted as the 7 black circles) from the unbranched outer portions of the glycogen molecule until only 4 glucosyl units (depicted as the 3 green circles and the 1 red circle) remain before an alpha1,6 branch point. The transferase component of debranching enzyme then transfers the 3 (green) glucose residues from the short branch to the end of an adjacent branch of the glycogen molecule. The glucosidase component of debranching enzyme then removes the glucose moiety (depicted as the red circle) remaining at the alpha1,6 branch point. In the process, the branch point formed by the alpha1,6 glucosidic bond is removed, hence the name debrancher.Unlike phosphorylase, which removes glucose moieties from glycogen in the form of glucose-1-phosphate, debrancher releases 1 free glucose moiety from each branch point. After the cleavage of the branch site, phosphorylase attacks unbranched portions of the glycogen molecule until the enzyme is stymied by the appearance of another branch point, at which point debranching enzyme once again is called into play. Eventually, large portions of the glycogen molecule are degraded to free glucose by the action of the amylo-alpha1,6-glucosidase activity of debranching enzyme and to glucose-1-phosphate by the action of phosphorylase.
Schematic representation of a portion of a molecule of glycogen. Open circles represent the glucose moieties connected to each other via alpha1,4 linkages. Solid circles represent the glucose moieties connected to their neighbors via alpha1,6 linkages. Thus, each solid circle represents a branch point in the molecule.
 
 
 
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