Genetics of Glycogen-Storage Disease Type I Clinical Presentation

  • Author: Karl S Roth, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Apr 16, 2012
 

History

  • Initial symptoms of neonatal hypoglycemia occur shortly after birth in patients with glycogen-storage disease type I (GSD I), and patients do not respond to glucagon administration. Symptoms include the following:
    • Tremors
    • Irritability
    • Cyanosis
    • Seizures
    • Apnea
    • Coma
  • Older infants may present with the following:
    • Frequent lethargy
    • Difficult arousal from overnight sleep
    • Tremors
    • Overwhelming hunger
    • Poor growth
    • Apparent increase in abdominal girth, although extremities appear thin
    • A doll-like facial appearance caused by adipose tissue deposition in the cheeks
  • Young children with glycogen-storage disease type Ia may experience nosebleeds.
  • Young children with glycogen-storage disease Ib may have frequent otitides, gingivitis, and boils.
  • Symptoms of severe hypoglycemia in patients of all ages are likely to follow any illness that causes mild anorexia or fasting (eg, viral gastroenteritis).
  • In middle childhood, patients may manifest evidence of rickets and anemia.
  • Patients with glycogen-storage disease Ib at all ages may be affected by a Crohnlike ileocolitis (pseudocolitis). The severity of the primary disorder is not correlated with the intestinal symptoms.
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Physical

  • Affected infants are healthy at birth, although some are born with an enlarged liver.
    • Careful abdominal examination is mandatory for any neonate with hypoglycemia.
    • Abdominal protuberance develops early because of massive hepatomegaly.
    • Splenomegaly does not occur.
    • The liver is firm and uniform in consistency in early life but may become nodular with the development of adenoma.
  • The patient may present with poor growth, short stature, and rachitic changes.
  • Gingivitis and compromised dentition may be present.
  • Xanthoma may be found on extensor surfaces, such as the elbows and knees.
  • Ultrasonography may reveal large kidneys in patients of all ages. Proteinuria may accompany this finding.
  • In addition to hypoglycemia, an increased plasma lactate value is a characteristic laboratory finding in a symptomatic newborn with glycogen-storage disease I. The increased lactate originates from the flooding of the glycolytic pathway by glucose-6-phosphate, which is derived from breakdown of glycogen, cannot be cleaved to free glucose, and is released into blood.
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Causes

  • Glycogen-storage disease Ia and Ib are autosomal recessive genetic traits caused by mutations at loci 17q21 and 11q23, respectively.
  • Glycogen-storage disease Ia is caused by deficient activity of the enzyme glucose-6-phosphatase, representing at least 14 distinct allelic variants.
  • Glycogen-storage disease Ib is caused by deficiency of glucose-6-phosphate translocase, which is responsible for importing glucose-6-phosphate from the cytosol to the interior of the microsome, thus bringing substrate into contact with enzyme. To date, allelic variation in this disorder has not been explored.
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Contributor Information and Disclosures
Author

Karl S Roth, MD  Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research

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.

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Microsome is shown in relation to the substrate, glucose-6-phosphate, which has been released from cytosolic glycogen. This substrate is transferred across the microsomal membrane by the protein translocase, where by glucose-6-phosphatase acts on it to release free glucose and inorganic phosphate. Patients with glycogen-storage disease type Ia are genetically deficient in glucose-6-phosphate activity, while those affected with glycogen-storage disease type Ib lack translocase.
 
 
 
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