Type VI Glycogen Storage Disease
- Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: George T Griffing, MD more...
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.[1, 2]
The following list contains a quick reference for 8 of the GSD types:
0 - Glycogen synthase deficiency
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 (Tauri disease)
The chart below demonstrates where various forms of GSD affect metabolic carbohydrate pathways.
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 necessarily 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 (also known as acid maltase deficiency), 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 patient history and physical examination, muscle biopsy, electromyography, ischemic forearm testing, and creatine kinase testing. Biochemical assay for enzyme activity is the method of definitive diagnosis.
In patients with Hers disease, defective liver phosphorylase results in hepatomegaly and hypoglycemia. The liver phosphorylase enzyme is found in the liver and in red blood cells.
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. Liver phosphorylase, which is found in the liver and red blood cells, is deficient, which results in glycogen accumulation in the liver and subsequent hypoglycemia.
Several mutations of the liver glycogen phosphorylase gene are reported.
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.
Morbidity results from consequences of hepatomegaly.
In general, GSDs present in childhood. Later onset correlates with a less severe form. Consider Pompe disease if onset is in infancy.
Brown LM, Corrado MM, van der Ende RM, Derks TG, Chen MA, Siegel S, et al. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children. J Inherit Metab Dis. 2014 Jul 29. [Medline].
Parker EI, Xing M, Moreno-De-Luca A, Harmouche E, Terk MR. Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders. Br J Radiol. 2014 Jan. 87(1033):20130467. [Medline]. [Full Text].
Manzia TM, Angelico R, Toti L, Cillis A, Ciano P, Orlando G, et al. Glycogen storage disease type Ia and VI associated with hepatocellular carcinoma: two case reports. Transplant Proc. 2011 May. 43(4):1181-3. [Medline].
Zingone A, Hiraiwa H, Pan CJ. Correction of glycogen storage disease type 1a in a mouse model by gene therapy. J Biol Chem. 2000 Jan 14. 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. 1999 Nov. 189(3):416-24. [Medline].
Asami T, Kikuchi T, Asami K. Effect of clonidine on the height of a child with glycogen storage disease type VI: a 13 year follow-up study. Acta Paediatr Jpn. 1996 Oct. 38(5):524-8. [Medline].
Ji HF, Wang WL, Shen Y, et al. Reduced-size liver transplantation for glycogen storage disease. Hepatobiliary Pancreat Dis Int. 2009 Feb. 8(1):106-8. [Medline].
Amato AA. Acid maltase deficiency and related myopathies. Neurol Clin. 2000 Feb. 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. 2000 Jan. 105(1):e10. [Medline].
Burwinkel B, Bakker HD, Herschkovitz E. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet. 1998 Apr. 62(4):785-91. [Medline].
Chen Y. Glycogen Storage Diseases. Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2000. Vol 1: 1537-8.
DiMauro S, Bruno C. Glycogen storage diseases of muscle. Curr Opin Neurol. 1998 Oct. 11(5):477-84. [Medline].
Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc. 1993 Dec. 93(12):1423-30. [Medline].
Orho M, Bosshard NU, Buist NR. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. J Clin Invest. 1998 Aug 1. 102(3):507-15. [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. 1982 Dec 27. 150(2):489-93. [Medline].
Tang NL, Hui J, Young E, et al. A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity. Mol Genet Metab. 2003 Jun. 79(2):142-5. [Medline].
Wolfsdorf JI, Holm IA, Weinstein DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am. 1999 Dec. 28(4):801-23. [Medline].