Disorders of carbohydrate metabolism

Disease related to glycolysis

Pyruvate kinase deficiency

Cause of pyruvate kinase deficiency

Mutation of pyruvate kinase gene (PKLR)

Conseuquence of pyruvate kinase deficiency

Accumulation of glycolytic intermediates, ATP production/NADH regeneration deficiency

Symptoms of pyruvate kinase deficiency

Hemolytic anemia and jaundice

Hemolytic anemia

Premature destruction of RBCs in the spleen/liver

Bilirubin

Metabolite of hemes released from RBC damage

Jaundice

Livers not fully developed -> cannot conjugate bilirubin

Disease related to TCA cycle

Pyruvate dehydrogenase deficiency

Consequences of pyruvate dehydrogenase deficiency

Accumulation of lactate and ATP production deficiency

Symptoms of pyruvate dehydrogenase deficiency

Lactic acidosis, lethargy, neurological symptoms

Disease related to gluconeogenesis

Hepatic Fructose 1,6-biphosphatase deficiency

Cause of Hepatic Fructose 1,6-biphosphatase deficiency

Mutation of fructose 1,6-biphosphatase gene (FBP1)

Consequences of Hepatic Fructose 1,6-biphosphatase deficiency

Decreased glucose production from non-carbohydrate sources, accumulation of lactate

Symptoms of Hepatic Fructose 1,6-biphosphatase deficiency

Fasting hypoglycemia, lactic acidosis

Disease related to pentose phosphate pathway

Glucose 6-phosphate dehydrogenase deficiency (G6PD deficiency)

Cause of G6PD deficiency

X-linked recessive disease

Consequences of G6PD deficiency

Accumulation of reactive oxygen species -> oxidative stress -> cell death

Symptoms of G6PD deficiency

Hemolytic anemia, Hemoglobinuria (black urine), Jaundice

Individuals with G6PD deficiency are usually asymptomatic except when:

Exposed to oxidant stress (infection, java beans)

Disease related to glycogen metabolism

Von Gierke’s disease

Cause of Von Gierke’s disease

Mutation of glucose 6-phosphatase gene (G6PC)

Consequences of Von Gierke’s disease

Accumulation of glycogen in the liver

Symptoms of Von Gierke’s disease

Hepatomegaly, fasting hypoglycemia, lactic acidosis, hyperlipidemia

Hepatomegaly

Abnormal enlargement of the liver

Hyperlipidemia

Usage of fatty acids to generate energy -> high lipid levels in serum

Treatment for Von Gierke’s disease

• Frequent carbohydrate administration

• Uncooked cornstarch

• Drugs (fibrates or statins)

• Liver transplant

Diseases related to Galactose metabolism

Type 1-3 galactosemia

Cause of type 1 galactosemia

Mutation of galactose 1-phosphate uridyltransferase (GALT) gene

Consequences of type 1 galactosemia

Accumulation of galactose and galactose 1-phosphate

Consequence of galactose accumulation

Vomiting, diarrhea, unable to gain weight, cataracts, brain damage, renal failure

Consequence of galactose 1-phosphate accumulation

Hepatomegaly, jaundice, liver damage

Treatments of type 1 galactosemia

Avoid dairy products containing galactose

Cause of type 2 galactosemia

Mutation of galactokinase gene

Symptoms/treatment of type 2 galactosemia

Similar to type 1