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Glycogen Storage Disease, Type VII
Updated: Sep 21, 2007
Introduction
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)
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, often misprinted as Tauri 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, 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 recently 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.
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.
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.1
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.
Clinical
History
- Severity varies based on an individual's enzyme activity level.
- Symptoms include exercise intolerance (premature fatigability), weakness and stiffness with exercise, and painful muscle cramps. Symptoms resolve with rest.
- Exercise intolerance is noted in childhood much earlier and is more severe in Tarui disease than in McArdle disease. The second wind phenomenon is not seen in Tarui disease as it is in McArdle disease. Haller and Vissing concluded that the inability to properly metabolize blood glucose prevents the spontaneous second wind.2
- Exantus and colleagues report one case of acute renal failure secondary to rhabdomyolysis.3
- Finsterer and colleagues report on one patient followed for several years.4 Neurologic symptoms believed attributable to Tarui disease include complex partial seizures, diplopia, hyporeflexia, central facial palsy, and upper extremity weakness.
Physical
- Physical examination findings may be normal; therefore, clinical suspicion must be derived from patient history findings.
- Laboratory and procedural studies may be helpful.
Causes
Phosphofructokinase is made of 4 peptides. A genetic defect has been discovered in the muscle subunit locus.
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References
Haller RG, Vissing J. No spontaneous second wind in muscle phosphofructokinase deficiency. Neurology. Jan 13 2004;62(1):82-6. [Medline].
Haller RG, Vissing J. No spontaneous second wind in muscle phosphofructokinase deficiency. Neurology. Jan 13 2004;62(1):82-6. [Medline].
Exantus J, Ranchin B, Dubourg L, et al. Acute renal failure in a patient with phosphofructokinase deficiency. Pediatr Nephrol. Jan 2004;19(1):111-3. [Medline].
Finsterer J, Stöllberger C, Kopsa W. Neurologic and cardiac progression of glycogenosis type VII over an eight-year period. South Med J. Dec 2002;95(12):1436-40. [Medline].
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].
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].
Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. Feb 2000;18(1):151-65. [Medline].
Aminoff MJ, ed. Electromyography in Clinical Practice. 3rd ed. New York, NY: Churchill Livingstone; 1998.
Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. Jan 2000;105(1):e10. [Medline].
Chen Y. Glycogen Storage Diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 1. 8th ed. New York, NY: McGraw-Hill; 2000:1539-40.
DiMauro S, Bruno C. Glycogen storage diseases of muscle. Curr Opin Neurol. Oct 1998;11(5):477-84. [Medline].
Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc. Dec 1993;93(12):1423-30. [Medline].
Lin HC, Young C, Wang PJ. Muscle phosphofructokinase deficiency (Tarui''s disease): report of a case. J Formos Med Assoc. Mar 1999;98(3):205-8. [Medline].
Raben N, Sherman JB, Adams E. Various classes of mutations in patients with phosphofructokinase deficiency (Tarui''s disease). Muscle Nerve. 1995;3:S35-8. [Medline].
Smit GP, Fernandes J, Leonard JV. The long-term outcome of patients with glycogen storage diseases. J Inherit Metab Dis. 1990;13(4):411-8. [Medline].
Stevens AN, Iles RA, Morris PG. Detection of glycogen in a glycogen storage disease by 13C nuclear magnetic resonance. FEBS Lett. Dec 27 1982;150(2):489-93. [Medline].
Wolfsdorf JI, Holm IA, Weinstein DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am. Dec 1999;28(4):801-23. [Medline].
Further Reading
Keywords
Tarui disease, Tarui’s disease, Tauri disease, Tauri’s disease, GSD type VII, muscle phosphofructokinase deficiency, enzyme defect, glycogen storage disease, GSD, GSD type 0, glycogen synthase deficiency, GSD type Ia, glucose-6-phosphatase deficiency, G-6-P deficiency, von Gierke disease, GSD type II, acid maltase deficiency, Pompe disease, GSD type III, debranching enzyme deficiency, Forbes-Cori disease, GSD type IV, GSD type V, myophosphorylase deficiency, McArdle disease, transglucosidase deficiency, Andersen disease, amylopectinosis, GSD type VI, phosphorylase deficiency, Hers disease
