Type Ib Glycogen Storage Disease 

  • Author: Wayne E Anderson, DO; Chief Editor: George T Griffing, MD   more...
 
Updated: Jan 3, 2012
 

Background

A glycogen storage disease (GSD) is the result of an enzyme defect. These enzymes normally catalyze reactions that ultimately convert glycogen compounds to glucose. Enzyme deficiency results in glycogen accumulation in tissues. In many cases, the defect has systemic consequences, but, in some cases, the defect is limited to specific tissues. Most patients experience muscle symptoms, such as weakness and cramps, although certain GSDs manifest as specific syndromes, such as hypoglycemic seizures or cardiomegaly.

The image below illustrates the metabolic pathways for carbohydrates.

Metabolic pathways of carbohydrates. Metabolic pathways of carbohydrates.

Although at least 14 unique GSDs are discussed in the literature, the 4 that cause clinically significant muscle weakness are Pompe disease (GSD type II, acid maltase deficiency), Cori disease (GSD type III, debranching enzyme deficiency), McArdle disease (GSD type V, myophosphorylase deficiency), and Tarui disease (GSD type VII, phosphofructokinase deficiency). One form, Von Gierke disease (GSD type Ia, glucose-6-phosphatase deficiency), causes clinically significant end-organ disease with significant morbidity. The remaining GSDs are not benign but are less clinically significant; therefore, the physician should consider the aforementioned GSDs when initially entertaining the diagnosis of a GSD. Interestingly, there also is a GSD type 0, which is due to defective glycogen synthase.

These inherited enzyme defects usually present in childhood, although some, such as McArdle disease and Pompe disease, have separate adult-onset forms. In general, GSDs are inherited as autosomal recessive conditions. Several different mutations have been reported for each disorder.

Unfortunately, no specific treatment or cure exists, although diet therapy may be highly effective at reducing clinical manifestations.[1] In some cases, liver transplantation may abolish biochemical abnormalities. Active research continues.

Diagnosis depends on muscle biopsy, electromyelography, ischemic forearm test, creatine kinase levels, patient history, and physical examination. Biochemical assay for enzyme activity is the method of definitive diagnosis.

Acid maltase catalyzes the hydrogenation reaction of maltose to glucose. Acid maltase deficiency is a unique glycogenosis since glycogen accumulation is lysosomal rather than in the cytoplasm. It also has a unique clinical presentation depending on age at onset, ranging from fatal hypotonia and cardiomegaly in the neonate to muscular dystrophy in adults.

Glucose-6-phosphatase (G-6-P) is the specific enzyme deficiency in Von Gierke disease. GSD type 1b is a similar condition with a defective G-6-P transporter protein.[2, 3] A newly described form, GSD type 1c, is not thought to be related to a transporter protein mutation.

Recent research

In a 2-year study of 7 patients with GSD type Ib, Melis et al examined whether the administration of vitamin E could improve or prevent the clinical manifestations of neutropenia and neutrophil dysfunction.[4] Vitamin E supplementation was provided to patients only during the second year of the study, and neutrophil counts from the first and second years were compared. The investigators found that during the second year, mean neutrophil counts were significantly greater than they were during the first. Reductions in the frequency and severity of infections, mouth ulcers, and perianal lesions also occurred during the second year. However, no changes in neutrophil function were found in association with vitamin E supplementation.

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Pathophysiology

With an enzyme defect, carbohydrate metabolic pathways are blocked, and excess glycogen accumulates in affected tissues. Each GSD represents a specific enzyme defect, and each enzyme is in specific, or most, body tissues. The G-6-P transporter protein is found in the liver and kidney.

GSD type Ib is an autosomal recessive condition.

Glucose-6-phosphate is an intermediate in glycogen synthesis and glucose metabolism. GSD type Ib differs from GSD type Ia in that it is not explained by mutations of the phosphohydrolase gene. Veiga-da-Cuhna and colleagues provide evidence that all non-1a cases can be explained by mutations of the glucose-6-phosphate translocase gene.[5]

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Epidemiology

Frequency

International

Herling and colleagues studied the incidence and frequency of inherited metabolic conditions in British Columbia. GSDs are found in 2.3 children per 100,000 births per year.

Mortality/Morbidity

  • GSD Ib, unlike GSD Ia, involves bacterial infections including brain abscesses. However, D'Eufemia and colleagues report one case of a 10-year-old boy with GSD II with neutropenia and neutrophil dysfunction but without severe recurrent infections.[6]
  • Immediate morbidity arises from hypoglycemic seizures.
  • Serious long-term complications include nephropathy and hepatic adenoma.

Age

  • In general, GSDs present in childhood. Later onset correlates with a less severe form. Consider Pompe disease if onset is in infancy.
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Contributor Information and Disclosures
Author

Wayne E Anderson, DO  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 is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Law, Medicine & Ethics, California Medical Association, and San Francisco Medical Society

Disclosure: Cephalon Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; King Honoraria Speaking and teaching; Forest Honoraria Speaking and teaching

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor 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, 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, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

References

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