Disorders of Carbohydrate Absorption, Transmembrane Transport and Metabolism

Carbohydrates are an important source of energy in the
human organism. Within the body, glucose is the most
abundant monosaccharide that can be stored as glycogen,
a branched polymer with a protein core (glycogenin),
mainly in liver and muscle. Inborn errors of metabolism
may affect the uptake, distribution and reabsorption of monosaccharides in different organs, a process that is
meticulously regulated by a system of transporter proteins.
Congenital disorders may impair the intestinal
digestion of disaccharides and the conversion of monosaccharides
(fructose, galactose) into glucose. They can
further affect glycogen synthesis, glycogen breakdown
(glycogenolysis), glucose metabolism to acetyl-CoA
(glycolysis) and de novo synthesis of glucose
(gluconeogenesis).
Glucose absorption and transport disorders present
with a very variable clinical picture depending on which
of the organ- and substrate-specific transporters is
affected. Likewise, disorders of galactose and fructose
metabolism affect different organs due to the accumulation
of toxic intermediates. After the introduction of these
monosaccharides with the diet, impaired liver function is
frequently among the first signs.
Glycogen storage diseases can be divided into those
mainly presenting with hepatic manifestations (hepatomegaly,
fasting intolerance, 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 signs, for example, haemolytic
anaemia, may be observed depending on 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
di- or monosaccharides. Outcome, however, is highly
variable and mainly depends on the underlying type of
disorder. Causal treatment is not available for most diseases
and for some patients, organ transplantation (liver,
kidney, heart) is an option. Experimental treatments may
include enzyme replacement therapy (available, e.g., for
lysosomal α-glucosidase deficiency, GSD-IIa) and gene
therapy.