Type VII Glycogen Storage Disease

Updated: Aug 25, 2014
  • Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: George T Griffing, MD  more...
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Overview

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 following list contains a quick reference for 8 of the GSD types:

  • 0 - Glycogen synthase deficiency
  • Ia - Glucose-6-phosphatase deficiency (von Gierke disease)
  • II - Acid maltase deficiency (Pompe disease)
  • III - Debranching enzyme deficiency (Forbes-Cori disease)
  • IV - Transglucosidase deficiency (Andersen disease, amylopectinosis)
  • V - Myophosphorylase deficiency (McArdle disease)
  • VI - Phosphorylase deficiency (Hers disease)
  • VII - Phosphofructokinase deficiency (Tarui disease)

The chart below demonstrates where various forms of GSD affect the metabolic carbohydrate pathways.

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), which is often misspelled as Tauri disease. 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, GSD type 0 also is described, 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. In some cases, liver transplantation may abolish biochemical abnormalities. Active research continues.

Diagnosis depends on findings from muscle biopsy, electromyography, ischemic forearm testing, creatine kinase testing, patient history, and physical examination. Biochemical assay for enzyme activity is the method of definitive diagnosis.

Phosphofructokinase catalyzes the rate-limiting step in glycolysis. Phosphofructokinase deficiency leads to muscle pain and exercise-induced fatigue and weakness. Tarui disease resolves with rest, and, although no specific treatment exists, the condition may not progress to severe disability.

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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. Phosphofructokinase catalyzes the rate-limiting step in glycolysis. Enzyme deficiency decreases the rate of conversion of fructose-6-phosphate to fructose-1,6-diphosphate. Phosphofructokinase is found in muscle tissue and red blood cells.

Tarui disease is an autosomal recessive condition.

Garcia et al investigated the effects of phosphofructokinase deficiency in tissue other than skeletal muscle on the pathogenesis of GSD type VII. [1] In a study of phosphofructokinase-deficient mice, the authors found that because the animals' erythrocytes retained only 50% of their phosphofructokinase activity, severe hemolysis, significant decreases in 2,3-bisphosphoglycerate levels (impairing the extraction of oxygen from hemoglobin), and compensatory reticulocytosis and splenomegaly occurred. Reduced levels of cardiac phosphofructokinase activity were found as well, which, combined with the other hematologic changes, led to the development of cardiac hypertrophy.

Madhoun et al reported a unique case of a man with phosphofructokinase deficiency who also presented with portal and mesenteric vein thrombosis. [2]

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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

As in McArdle disease, immediate morbidity arises from exercise intolerance.

Unlike in McArdle disease, Haller and Vissing found no consistent second wind phenomenon in GSD VII. [3]

Race

The disease appears to be prevalent among people of Ashkenazi Jewish descent.

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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