Reversal of glycogen storage disease type IIIa-related cardiomyopathy with modification of diet
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Glycogen storage disease type III (GSD III) is caused by a deficiency in debranching enzyme, which leads to an accumulation of abnormal glycogen called limit dextrin in affected tissues. Muscle and liver involvement is present in GSD type IIIa, while the defect is limited to the liver only in GSD type IIIb. Besides skeletal muscle involvement, a cardiomyopathy resembling idiopathic hypertrophic cardiomyopathy is seen. Management consists of maintaining normoglycaemia by supplementation with cornstarch therapy and/or protein. While studies are lacking regarding the best treatment for skeletal muscle disease, a high-protein diet was previously reported to be beneficial. No cases of improvement in cardiomyopathy have been reported. Our patient presented in infancy with hypoglycaemia and hepatomegaly. His prescribed management consisted of cornstarch supplementation and a high-protein diet providing 20% of his total energy needs. At 16 years of age, he developed a severe cardiomyopathy with a left ventricular mass index of 209 g/m2. The cardiomyopathy remained stable on a protein intake of 20–25% of total energy. At age 22 years, the diet was changed to increase his protein intake to 30% of total energy and minimize his cornstarch therapy to only what was required to maintain normoglycaemia. Dramatic improvement in the cardiomyopathy occurred. Over one year, his left ventricular mass index decreased from 159.7 g/m2 to 78 g/m2 (normal 50–86 g/m2) and the creatine kinase levels decreased from 455 U/L to 282 U/L. Avoidance of overtreatment with carbohydrate and a high-protein diet can reverse and may prevent cardiomyopathy.
- Akazawa H, Kuroda T, Kim S, Mito H, Kojo T, Shimada K (1997) Specific heart muscle disease associated with glycogen storage disease type III: clinical similarity to the dilated phase of hypertrophic cardiomyopathy. Eur Heart J 18: 532–533. CrossRef
- Bao Y, Yang BZ, Dawson TL Jr, Chen YT (1997) Isolation and nucleotide sequence of human liver glycogen debranching enzyme mRNA: identification of multiple tissue-specific isoforms. Gene 197: 389–398. doi:10.1016/S0378-1119(97)00291-6. CrossRef
- Bates EJ, Heaton GM, Taylor C, Kernohan JC, Cohen P (1975) Debranching enzyme from rabbit skeletal muscle; evidence for the location of two active centres on a single polypeptide chain. FEBS Lett 58: 181–185. doi:10.1016/0014-5793(75)80254-7. CrossRef
- Carvalho JS, Matthews EE, Leonard JV, Deanfield J (1993) Cardiomyopathy of glycogen storage disease type III. Heart Vessels 8: 155–159. doi:10.1007/BF01744800. CrossRef
- Chen YT (2001) Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 1521–1551.
- Coleman RA, Winter HS, Wolf B, Gilchrist JM, Chen YT (1992) Glycogen storage disease type III (glycogen debranching enzyme deficiency): correlation of biochemical defects with myopathy and cardiomyopathy. Ann Intern Med 116: 896–900.
- DiMauro S, Hartwig GB, Hays A, et al (1979) Debrancher deficiency: neuromuscular disorder in 5 adults. Ann Neurol 5: 422-436. doi:10.1002/ana.410050504. CrossRef
- Fellows IW, Lowe JS, Ogilvie AL, Stevens A, Toghill PJ, Atkinson M (1983) Type III glycogenosis presenting as liver disease in adults with atypical histological features. J Clin Pathol 36: 431–434. doi:10.1136/jcp.36.4.431. CrossRef
- Kiechl S, Willeit J, Vogel W, Kohlendorfer U, Poewe W (1999) Reversible severe myopathy of respiratory muscles due to adult-onset type III glycogenosis. Neuromuscul Disord 9: 408–410. doi:10.1016/S0960-8966(99)00038-3. CrossRef
- Labrune P, Huguet P, Odievre M (1991) Cardiomyopathy in glycogen-storage disease type III: clinical and echographic study of 18 patients. Pediatr Cardiol 12: 161–163. doi:10.1007/BF02238523. CrossRef
- Lee PJ, Deanfield JE, Burch M, Baig K, McKenna WJ, Leonard JV (1997) Comparison of the functional significance of left ventricular hypertrophy in hypertrophic cardiomyopathy and glycogenosis type III. Am J Cardiol 79: 834–838. doi:10.1016/S0002-9149(96)00885-5. CrossRef
- Liu W, Madsen NB, Braun C, Withers SG (1991) Reassessment of the catalytic mechanism of glycogen debranching enzyme. Biochemistry 30: 1419–1424. doi:10.1021/bi00219a036. CrossRef
- Miller CG, Alleyne GA, Brooks SE (1972) Gross cardiac involvement in glycogen storage disease type 3. Br Heart J 34: 862–864. doi:10.1136/hrt.34.8.862. CrossRef
- Momoi T, Sano H, Yamanaka C, Sasaki H, Mikawa H (1992) Glycogen storage disease type III with muscle involvement: reappraisal of phenotypic variability and prognosis. Am J Med Genet 42: 696–699. doi:10.1002/ajmg.1320420514. CrossRef
- Moses SW, Wanderman KL, Myroz A, Frydman M (1989) Cardiac involvement in glycogen storage disease type III. Eur J Pediatr 148: 764–766. doi:10.1007/BF00443106. CrossRef
- Olson LJ, Reeder GS, Noller KL, Edwards WD, Howell RR, Michels VV (1984) Cardiac involvement in glycogen storage disease III: morphologic and biochemical characterization with endomyocardial biopsy. Am J Cardiol 53: 980–981. doi:10.1016/0002-9149(84)90551-4. CrossRef
- Rossignol AM, Meyer M, Rossignol B, Palcoux MP, Raynaud EJ, Bost M (1979) Glycogenosis type III myocardiopathy. Arch Fr Pediatr 36: 303–309.
- Shen J, Bao Y, Liu HM, Lee P, Leonard JV, Chen YT (1996) Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle. J Clin Invest 98: 352–357. doi:10.1172/JCI118799. CrossRef
- Slonim AE, Weisberg C, Benke P, Evans OB, Burr IM (1982) Reversal of debrancher deficiency myopathy by the use of high-protein nutrition. Ann Neurol 11: 420–422. doi:10.1002/ana.410110417. CrossRef
- Slonim AE, Coleman RA, Moses WS (1984) Myopathy and growth failure in debrancher deficiency: improvement with high-protein nocturnal enteral therapy. J Pediatr 105: 906–911. doi:10.1016/S0022-3476(84)80075-X. CrossRef
- Talente GM, Coleman RA, Alter C, et al (1994) Glycogen storage disease in adults. Ann Intern Med 120: 218–226.
- Wolfsdorf JI, Weinstein DA (2003) Glycogen storage diseases. Rev Endocr Metab Disord 4: 95–102. doi:10.1023/A:1021831621210. CrossRef
- Reversal of glycogen storage disease type IIIa-related cardiomyopathy with modification of diet
Journal of Inherited Metabolic Disease
Volume 32, Issue 1 Supplement, pp 103-106
- Cover Date
- Print ISSN
- Online ISSN
- Springer Netherlands
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Raymond C. Philip Research and Education Unit, Division of Genetics, Department of Pediatrics, University of Florida, Gainesville, Florida, USA
- 3. Division of Pediatric Endocrinology and Glycogen Storage Disease Program, Department of Pediatrics, University of Florida, Gainesville, Florida, USA
- 4. Glycogen Storage Disease Program, University of Florida College of Medicine, Box 100296, Gainesville, FL, 32610-0296, USA
- 2. Division of Cardiology, Department of Pediatrics, University of Florida, Gainesville, Florida, USA