Carbohydrate metabolism disorders Notes

NOTES NOTES CARBOHYDRATE METABOLISM DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Inherited disorders of carbohydrate metabolism (fructose, glucose, galactose) ▪ Determined by exposure to external triggers (e.g. dietary factors) ▪ Disruption in certain metabolic pathways → accumulation of byproducts → systemic alterations, organ failures SIGNS & SYMPTOMS ▪ See individual disorders DIAGNOSIS LAB RESULTS ▪ Enzymatic dosage OTHER DIAGNOSTICS ▪ Genetic testing TREATMENT OTHER INTERVENTIONS ▪ Avoid triggers ESSENTIAL FRUCTOSURIA osms.it/essential-fructosuria PATHOLOGY & CAUSES ▪ Benign disease; impaired fructose metabolism → increased excretion in urine CAUSES ▪ Autosomal recessive mutation in fructokinase, AKA ketohexokinase (KHK) ▫ First enzyme in fructose metabolism ▪ Intake of fructose-rich food/fructose-related sugar (e.g. sucrose, sorbitol) → increase of fructose in blood → excretion of fructose in urine SIGNS & SYMPTOMS ▪ Asymptomatic 238 OSMOSIS.ORG DIAGNOSIS LAB RESULTS ▪ Positivity for reducing substances in urine TREATMENT OTHER INTERVENTIONS ▪ No treatment necessary

Chapter 41 Carbohydrate Metabolism Disorders GALACTOSEMIA osms.it/galactosemia PATHOLOGY & CAUSES ▪ Disease characterized by altered metabolism of galactose CAUSES ▪ Autosomal recessive disorder SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ FTT Vomiting, diarrhea with lactation Jaundice, hepatomegaly Cataract Intellectual disability, lethargy, speech disorder, altered muscle coordination (ataxia) Three possible mutations ▪ Galactose-1-phosphate uridyl transferase (GALT) deficiency (most common) ▫ Accumulation of galactose-1-phosphate + alternative metabolic pathway activation → accumulation of galactose metabolites (galactitol, galactonate) ▪ Galactokinase deficiency (uncommon) ▫ Less severe, often asymptomatic ▪ Uridine diphosphate (UDP) galactose-4epimerase deficiency (uncommon) LAB RESULTS COMPLICATIONS OTHER INTERVENTIONS ▪ Metabolites accumulate in ▫ Eyes: increasing osmotic pressure → water attraction → opacification of lens (cataract) ▫ Liver: fatty alteration, cirrhosis ▫ Brain: cell damage, edema, gliosis ▫ Kidney: prevent amino acid reabsorption → aminoaciduria ▪ Altered neutrophil activity → increased risk of sepsis from E.coli ▪ Gonadal failure, hemolysis, coagulopathy DIAGNOSIS ▪ Routinely screened in newborns ▫ Dosage of enzymes involved in galactose metabolism TREATMENT ▪ Elimination of galactose from diet OSMOSIS.ORG 239

HEREDITARY FRUCTOSE INTOLERANCE osms.it/hereditary-fructose-intolerance PATHOLOGY & CAUSES ▪ Disease characterized by alteration of fructose metabolism CAUSES ▪ Autosomal recessive mutation in liver aldolase (aldolase B) ▪ Aldolase B deficiency → fructose 1-phosphate buildup → ▫ Local fructose toxicity → liver cell death ▫ Hypoglycemia ▫ Adenosine triphosphate (ATP), phosphate depletion → inhibition of protein synthesis → hepatic, renal damage SIGNS & SYMPTOMS ▪ Avoidance of foods containing fructose (e.g. fruit, juice) ▪ Acute ingestion of fructose/compounds which contain fructose (e.g. sucrose, sorbitol) → nausea, vomiting; restlessness; pallor; sweating, trembling; lethargy, apathy; convulsions; coma ▪ Repeated ingestion of fructose → failure to thrive (FTT); liver disease (e.g. jaundice, hepatomegaly); kidney disease 240 OSMOSIS.ORG DIAGNOSIS OTHER DIAGNOSTICS ▪ Nutritional history, clinical presentation ▪ Genetic testing TREATMENT OTHER INTERVENTIONS ▪ Elimination of fructose from diet