Carbohydrates are one of the most important sources of energy in the human organism. Within the body, glucose is the most abundant monosaccharide which can be stored as glycogen, a branched polymer, in liver and muscle. Inborn errors of metabolism may affect the uptake, distribution and reabsorption of monosaccharides in different organs, a process which is meticulously regulated by a system of transporter proteins. Congenital disorders may impair the conversion of other monosaccharides (fructose, galactose) into glucose. They can further affect glycogen formation, glycogen breakdown (glycogenolysis), glucose metabolism to acetyl-CoA (glycolysis) and de novo synthesis of glucose from glucoplastic amino acids or from lactate (gluconeogenesis).
Glucose transport disorders present with a very variable clinical picture depending on which of the organ- and substrate-specific transporters are affected. This group of disorders includes intestinal glucose-galactose malabsorption, renal glucosuria, glucose transporter-1 deficiency of the blood-brain barrier and Fanconi-Bickel syndrome (a disease with hepatic glycogen storage and massive renal tubular malabsorption of glucose and other substances).
Disorders of fructose and galactose metabolism affect different organs because of the accumulation of toxic intermediates. After these monosaccharides have been introduced with the diet, symptoms secondary to impaired liver function are frequently the first signs.
Glycogen storage diseases can be divided into those mainly presenting with hepatic manifestations (hepatomegaly, hypoglycaemia) and those with muscular presentations (exertion intolerance, rhabdomyolysis). Some show a combination of these symptoms, cardiomyopathy may be an additional feature, and further accompanying symptoms, e.g. haemolytic anaemia, may be observed depending on the tissue distribution of the affected protein.
Management of most carbohydrate disorders requires symptomatic measures, supportive care and a multidisciplinary approach. In some conditions, dietetic treatment is possible which may have its basis in an exclusion of certain monosaccharides. A ketogenic diet supplying non-carbohydrate energy sources may have dramatic effects in glucose transporter-1 deficiency, and frequent meals or the administration of slowly absorbed carbohydrates are successful means to avoid hypoglycaemia in disorders with impaired endogenous glucose production. Outcome, however, is very variable and mainly depends on the underlying type of disorder. A causal treatment is not available for most types of carbohydrate disorders. Enzyme replacement therapy (with as yet unsatisfactory results) is only available for lysosomal α-glucosidase deficiency (GSD-IIa). In some patients with severe types of disorders or an unfavourable course, organ transplantation (liver, kidney, heart) is the only option for long-term survival.
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