Inborn errors of carbohydrate metabolism

Rana F. Ammoury, Fayez K. Ghishan

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


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. 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].

Original languageEnglish (US)
Title of host publicationLiver Disease in Children, Fourth Edition
PublisherCambridge University Press
Number of pages30
ISBN (Electronic)9781139012102
ISBN (Print)9781107013797
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Inborn errors of carbohydrate metabolism'. Together they form a unique fingerprint.

Cite this