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Glycogen debrancher deficiency (glycogen storage disease III)

Authors
William J Craigen, MD, PhD
Basil T Darras, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Glycogen is the stored form of glucose and serves as a buffer for glucose needs. It is composed of long polymers of a 1-4 linked glucose, interrupted by a 1-6 linked branch point every 4 to 10 residues. Glycogen is formed in periods of dietary carbohydrate loading and broken down when glucose demand is high or dietary availability is low (figure 1).

There are a number of inborn errors of glycogen metabolism that result from mutations in genes for virtually all of the proteins involved in glycogen synthesis, degradation, or regulation. Those disorders that result in abnormal storage of glycogen are known as glycogen storage diseases (GSDs). They have largely been categorized by number according to the chronology of recognition of the responsible enzyme defect (table 1). The age of onset varies from in utero to adulthood.

Glycogen is most abundant in liver and muscle, which are most affected by these disorders. The physiologic importance of a given enzyme in liver and muscle determines the clinical manifestations of the disease.

The main role of glycogen in the liver is to store glucose for release to tissues that are unable to synthesize significant amounts during fasting. The major manifestations of disorders of glycogen metabolism affecting the liver are hypoglycemia and hepatomegaly. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus".)

Glycogen serves as the primary source of energy for high-intensity muscle activity by providing substrates for the generation of adenosine triphosphate (ATP). The major manifestations of disorders of glycogen metabolism affecting muscle are muscle cramps, exercise intolerance and easy fatigability, and progressive weakness.

      

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Literature review current through: Nov 2016. | This topic last updated: Wed Oct 12 00:00:00 GMT+00:00 2016.
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References
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  1. Lucchiari S, Fogh I, Prelle A, et al. Clinical and genetic variability of glycogen storage disease type IIIa: seven novel AGL gene mutations in the Mediterranean area. Am J Med Genet 2002; 109:183.
  2. Yang-Feng TL, Zheng K, Yu J, et al. Assignment of the human glycogen debrancher gene to chromosome 1p21. Genomics 1992; 13:931.
  3. Yang BZ, Ding JH, Enghild JJ, et al. Molecular cloning and nucleotide sequence of cDNA encoding human muscle glycogen debranching enzyme. J Biol Chem 1992; 267:9294.
  4. Bao Y, Dawson TL Jr, Chen YT. Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking region. Genomics 1996; 38:155.
  5. Rousseau-Nepton I, Okubo M, Grabs R, et al. A founder AGL mutation causing glycogen storage disease type IIIa in Inuit identified through whole-exome sequencing: a case series. CMAJ 2015; 187:E68.
  6. Santer R, Kinner M, Steuerwald U, et al. Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands. Eur J Hum Genet 2001; 9:388.
  7. Parvari R, Moses S, Shen J, et al. A single-base deletion in the 3'-coding region of glycogen-debranching enzyme is prevalent in glycogen storage disease type IIIA in a population of North African Jewish patients. Eur J Hum Genet 1997; 5:266.
  8. Aoyama Y, Ozer I, Demirkol M, et al. Molecular features of 23 patients with glycogen storage disease type III in Turkey: a novel mutation p.R1147G associated with isolated glucosidase deficiency, along with 9 AGL mutations. J Hum Genet 2009; 54:681.
  9. Geberhiwot T, Alger S, McKiernan P, et al. Serum lipid and lipoprotein profile of patients with glycogen storage disease types I, III and IX. J Inherit Metab Dis 2007; 30:406.
  10. Hershkovitz E, Forschner I, Mandel H, et al. Glycogen storage disease type III in Israel: presentation and long-term outcome. Pediatr Endocrinol Rev 2014; 11:318.
  11. Labrune P, Trioche P, Duvaltier I, et al. Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature. J Pediatr Gastroenterol Nutr 1997; 24:276.
  12. Oterdoom LH, Verweij KE, Biermann K, et al. Hepatocellular Adenomas and Carcinoma in Asymptomatic, Non-Cirrhotic Type III Glycogen Storage Disease. J Gastrointestin Liver Dis 2015; 24:515.
  13. Markowitz AJ, Chen YT, Muenzer J, et al. A man with type III glycogenosis associated with cirrhosis and portal hypertension. Gastroenterology 1993; 105:1882.
  14. DiMauro S, Hartwig GB, Hays A, et al. Debrancher deficiency: neuromuscular disorder in 5 adults. Ann Neurol 1979; 5:422.
  15. Murase T, Ikeda H, Muro T, et al. Myopathy associated with type 3 glycogenosis. J Neurol Sci 1973; 20:287.
  16. Moses SW, Gadoth N, Bashan N, et al. Neuromuscular involvement in glycogen storage disease type III. Acta Paediatr Scand 1986; 75:289.
  17. Brunberg JA, McCormick WF, Schochet SS. Type 3 glycogenosis. An adult with diffuse weakness and muscle wasting. Arch Neurol 1971; 25:171.
  18. Ugawa Y, Inoue K, Takemura T, Iwamasa T. Accumulation of glycogen in sural nerve axons in adult-onset type III glycogenosis. Ann Neurol 1986; 19:294.
  19. Michon CC, Gargiulo M, Hahn-Barma V, et al. Cognitive profile of patients with glycogen storage disease type III: a clinical description of seven cases. J Inherit Metab Dis 2015; 38:573.
  20. Austin SL, Proia AD, Spencer-Manzon MJ, et al. Cardiac Pathology in Glycogen Storage Disease Type III. JIMD Rep 2012; 6:65.
  21. Cuspidi C, Sampieri L, Pelizzoli S, et al. Obstructive hypertrophic cardiomyopathy in type III glycogen-storage disease. Acta Cardiol 1997; 52:117.
  22. Akazawa H, Kuroda T, Kim S, et al. Specific heart muscle disease associated with glycogen storage disease type III: clinical similarity to the dilated phase of hypertrophic cardiomyopathy. Eur Heart J 1997; 18:532.
  23. Ogimoto A, Okubo M, Okayama H, et al. A Japanese patient with cardiomyopathy caused by a novel mutation R285X in the AGL gene. Circ J 2007; 71:1653.
  24. Cabrera-Abreu J, Crabtree NJ, Elias E, et al. Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX. J Inherit Metab Dis 2004; 27:1.
  25. Hobson-Webb LD, Austin SL, Bali DS, Kishnani PS. The electrodiagnostic characteristics of Glycogen Storage Disease Type III. Genet Med 2010; 12:440.
  26. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc 1993; 93:1423.
  27. Dagli AI, Zori RT, McCune H, et al. Reversal of glycogen storage disease type IIIa-related cardiomyopathy with modification of diet. J Inherit Metab Dis 2009; 32 Suppl 1:S103.
  28. Brambilla A, Mannarino S, Pretese R, et al. Improvement of Cardiomyopathy After High-Fat Diet in Two Siblings with Glycogen Storage Disease Type III. JIMD Rep 2014; 17:91.
  29. Bhattacharya K, Orton RC, Qi X, et al. A novel starch for the treatment of glycogen storage diseases. J Inherit Metab Dis 2007; 30:350.
  30. Iyer SG, Chen CL, Wang CC, et al. Long-term results of living donor liver transplantation for glycogen storage disorders in children. Liver Transpl 2007; 13:848.
  31. Matern D, Starzl TE, Arnaout W, et al. Liver transplantation for glycogen storage disease types I, III, and IV. Eur J Pediatr 1999; 158 Suppl 2:S43.
  32. Sun B, Fredrickson K, Austin S, et al. Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for glycogen storage disease type III. Mol Genet Metab 2013; 108:145.
  33. Yi H, Brooks ED, Thurberg BL, et al. Correction of glycogen storage disease type III with rapamycin in a canine model. J Mol Med (Berl) 2014; 92:641.