Abstract
Introduction: Inherited metabolic disorders (IMD) of carbohydrates represent a heterogeneous group of >250 different diseases caused by impaired synthesis, transport or degradation of galactose, fructose, glucose, disaccharides, glycogen, glycosaminoglycans and glycoproteins/glycolipids. Individual IMD of carbohydrates are rare, but the overall incidence in the population is >1:5 000.
Their diagnosis, except galactosemia in some countries is not part of laboratory neonatal screening of IMD and depends on clinical suspicion, biochemical and haematological analyses, and indication of selective metabolic screening. Material and methods: We summarize our experiences with the clinical, diagnostic, and therapeutic aspects of the most common IMD of carbohydrates in >360 patients diagnosed at our institution.
Results: Clinical manifestations in children with IMD of carbohydrates are heterogeneous and may overlap with several diseases. The first symptoms of IMD of galactose and fructose begin with acute manifestations of liver failure with impaired renal tubular functions and Fanconi syndrome.
Most liver glycogenoses (GSD) begin with hepatomegaly, growth failure, attacks of hypoglycaemia after 2.5-3 hours of fasting, hepatopathy, dyslipidaemia and lactic acidosis, but also neutropenia (GSD Ib) or liver failure (GSD IV). Muscle glycogenoses are presented by hypotonia and cardiomyopathy (GSD II) and muscle weakness and myalgia with attacks of rhabdomyolysis (GSD V).
Hepatic and muscle GSD phenotype overlaps with phosphoglucomutase 1 deficiency. Glucose-galactose transport (GLUT2) disorder links GSD phenotype to nephropathy with Fanconi syndrome.
IMD of carbohydrates in complex molecules cause mucopolysaccharidoses (MPS) and congenital disorders of glycosylation (CDG). Clinically characteristic of the MPS and CDG group are craniofacial dysmorphy, encephalopathy, hepato/splenomegaly, growth disorder, bone deformities, involvement of the myocardium and heart valves, hernia, recurrent otitis, and chronic rhinitis.
Conclusion: Early diagnosis is essential for successful treatment. Dietary intervention includes a lactose-free and low-galactose diet (galactosemia), a low-fructose diet (fructose intolerance), an anti-hypoglycaemic regimen with the addition of uncooked starches (liver GSDs), increased protein intake (GSD III), or a ketogenic diet (GLUT1).
Some congenital disorders of glycosylation (CDG) can be treated with mannose or galactose. Enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation are used in the treatment of children with MPS.