UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

糖原脱支酶缺陷病(糖原累积病Ⅲ型)

Authors
William J Craigen, MD, PhD
Basil T Darras, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS
Translators
田景琰, 副主任医师

引言

糖原是葡萄糖的贮存形式，并充当机体需要葡萄糖时的缓冲储备。糖原是葡萄糖经α-1,4糖苷键连接形成的长链聚合物，每隔4-10个残基插入一个由α-1,6糖苷键连接的支链。糖原在膳食碳水化合物负荷期形成，在葡萄糖需求大或膳食中葡萄糖摄入量少时分解(图 1)。

编码参与糖原合成、分解或调节的几乎所有蛋白质的基因发生突变时，可导致多种遗传性糖原代谢病。这些导致糖原异常累积的疾病称为糖原累积病(glycogen storage disease, GSD)。它们主要按照发现相关酶缺陷的先后顺序以数字进行编号分类(表 1)。发病年龄从胎儿期到成年期不等。

糖原含量最丰富的是肝脏和肌肉，它们是GSD最常累及的部位。肝脏和肌肉中特定酶的生理学意义决定了疾病的临床表现。

●肝糖原的主要作用是贮存葡萄糖，以便在空腹期间机体不能合成大量葡萄糖时释放至组织。累及肝脏的糖原代谢障碍的主要表现是低血糖和肝肿大。 (参见“糖尿病患者和正常人对低血糖的生理应答”)

●糖原为ATP的生成提供底物，从而充当高强度肌肉活动的主要能量来源。累及肌肉的糖原代谢障碍的主要表现是肌肉痉挛、运动不耐受、易疲劳和进行性肌无力。

      

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-06 . | This topic last updated: 2016-10-12.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  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. Markowitz AJ, Chen YT, Muenzer J, et al. A man with type III glycogenosis associated with cirrhosis and portal hypertension. Gastroenterology 1993; 105:1882.
  13. DiMauro S, Hartwig GB, Hays A, et al. Debrancher deficiency: neuromuscular disorder in 5 adults. Ann Neurol 1979; 5:422.
  14. Murase T, Ikeda H, Muro T, et al. Myopathy associated with type 3 glycogenosis. J Neurol Sci 1973; 20:287.
  15. Moses SW, Gadoth N, Bashan N, et al. Neuromuscular involvement in glycogen storage disease type III. Acta Paediatr Scand 1986; 75:289.
  16. Brunberg JA, McCormick WF, Schochet SS. Type 3 glycogenosis. An adult with diffuse weakness and muscle wasting. Arch Neurol 1971; 25:171.
  17. 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.
  18. Austin SL, Proia AD, Spencer-Manzon MJ, et al. Cardiac Pathology in Glycogen Storage Disease Type III. JIMD Rep 2012; 6:65.
  19. Cuspidi C, Sampieri L, Pelizzoli S, et al. Obstructive hypertrophic cardiomyopathy in type III glycogen-storage disease. Acta Cardiol 1997; 52:117.
  20. 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.
  21. 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.
  22. 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.
  23. Hobson-Webb LD, Austin SL, Bali DS, Kishnani PS. The electrodiagnostic characteristics of Glycogen Storage Disease Type III. Genet Med 2010; 12:440.
  24. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc 1993; 93:1423.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.