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Chapter 27 - Inborn Errors of Carbohydrate Metabolism
- from Section IV - Metabolic Liver Disease
- Edited by Frederick J. Suchy, Ronald J. Sokol, William F. Balistreri
- Edited in association with Jorge A. Bezerra, Cara L. Mack, Benjamin L. Shneider
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- Book:
- Liver Disease in Children
- Published online:
- 19 January 2021
- Print publication:
- 18 March 2021, pp 455-483
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Summary
Inborn errors of carbohydrate metabolism that lead to hepatic dysfunction are represented mainly by galactosemia, hereditary fructose intolerance (HFI), and glycogen storage disease (GSD) types I, III, IV, VI and IX. Although not related to energy disorders, congenital disorders of glycosylation (CDG) can likewise be placed in this group. The clinical presentation of such patients includes varying degree of hypoglycemia, acidosis, growth failure, and hepatic dysfunction. Appropriate steps in obtaining clinical history, physical examination, and laboratory evaluation support the definitive diagnosis. Advances in biochemistry, molecular biology and genetics continuously increase our treatment options and the development of newer treatment strategies. This chapter highlights our current knowledge.
Chapter 27 - Inborn errors of carbohydrate metabolism
- from Section IV - Metabolic liver disease
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- By Rana F. Ammoury, Department of Gastroenterology and Nutrition, Steele Children’s Research Center, University of Arizona, Tucson, AZ, USA, Fayez K. Ghishan, Steele Children’s Research Center, University of Arizona, Tucson, AZ, USA
- Edited by Frederick J. Suchy, University of Colorado Medical Center, Ronald J. Sokol, University of Colorado Medical Center, William F. Balistreri
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- Book:
- Liver Disease in Children
- Published online:
- 05 March 2014
- Print publication:
- 20 February 2014, pp 435-464
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Summary
Introduction
Inborn errors of carbohydrate metabolism that lead to hepatic dysfunction are represented mainly by galactosemia, hereditary fructose intolerance (HFI), and glycogen storage disease (GSD) types I, III, and IV. The clinical presentation of such patients includes varying degrees of hypoglycemia, acidosis, growth failure, and hepatic dysfunction. Appropriate steps in obtaining clinical history, physical examination, and laboratory evaluation support a definitive diagnosis. Advances in biochemistry and molecular biology, which have made significant contributions toward better understanding of the molecular defects underlying these disorders, are anticipated to eventually result in the development of newer treatment strategies. This chapter highlights current knowledge.
Disorders of galactose metabolism
In 1935, Mason and Turner provided the first detailed characterization of a galactose-intolerant individual [1]. Since then, three distinct disorders of galactose metabolism and several variant forms of the disease have been identified. These disorders are transmitted by autosomal recessive inheritance and are expressed as a cellular deficiency of one of three enzymes in the metabolic pathway through which galactose is converted to glucose: galactose-1-phosphate uridyl transferase, galactokinase, and uridine diphosphate (UDP) galactose-4-epimerase. Since each of these conditions results in milk-induced galactosemia but represents three distinct biochemical entities, the terms transferase-deficiency galactosemia, galactokinase-deficiency galactosemia, and epimerase-deficiency galactosemia have traditionally been used to distinguish between the various forms of the disease. Each enzymatic defect associated with galactosemia results in a distinctive clinical presentation. Clinical manifestations of toxicity in transferase-deficiency galactosemia, the classic form of the disease, include malnutrition, growth failure, cataract formation, progressive liver disease, mental retardation, and ovarian failure [2]. Galactokinase deficiency, originally described by Gitzelmann in 1967, results primarily in cataract formation and galactosuria [3]. In most cases of UDP-galactose-4-epimerase deficiency, the defect is limited to erythrocytes and leukocytes; therefore, affected individuals display no clinical or laboratory manifestations of galactosemia [4]. In a variant form of epimerase deficiency galactosemia identified by Holton and colleagues in 1981, however, the defect is more generalized and results in a severe clinical presentation resembling the classic form of the disease [5].
25 - Inborn Errors of Carbohydrate Metabolism
- from SECTION IV - METABOLIC LIVER DISEASE
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- By Fayez K. Ghishan, M.D., Professor and Head, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona, Mona Zawaideh, M.D., Assistant Professor, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona
- Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
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- Book:
- Liver Disease in Children
- Published online:
- 18 December 2009
- Print publication:
- 07 May 2007, pp 595-625
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Summary
This chapter deals with three inborn errors of carbohydrate metabolism that lead to hepatic dysfunction: galactosemia, hereditary fructose intolerance (HFI), and glycogen storage disease (GSD) types I, III, and IV. The clinical presentation of such patients includes varying degrees of hypoglycemia, acidosis, growth failure, and hepatic dysfunction. Appropriate steps in obtaining clinical history, physical examination, and laboratory evaluation support a definitive diagnosis. Advances in biochemistry and molecular biology, which have made significant contributions toward better understanding of the molecular defects underlying these disorders, are anticipated to result eventually in the development of newer treatment strategies. The newer information is highlighted in this chapter.
GALACTOSEMIA
The first detailed characterization of a galactose-intolerant individual was provided by Mason and Turner in 1935 [1]. Since then, three distinct disorders of galactose metabolism and several variant forms of the disease have been identified. These disorders are transmitted by autosomal recessive inheritance and are expressed as a cellular deficiency of one of three enzymes in the metabolic pathway through which galactose is converted to glucose: galactose-1-phosphate uridyl transferase, galactokinase, and uridine diphosphate (UDP) galactose-4-epimerase. The terms transferase deficiency galactosemia, galactokinase deficiency galactosemia, and epimerase deficiency galactosemia traditionally have been used to distinguish between the various forms of the disease. Until recently, the genetic basis of galactosemia was discerned primarily through quantification of red cell activity of these enzymes.
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