Carbohydrate Metabolic Disorders Notes

Carbohydrate Metabolic Disorders

Glycogen Storage Diseases

  • Caused by deficiencies of enzymes involved in glycogen synthesis.
  • Can cause hypoglycemia or deposition of abnormal amounts or types of glycogen in tissues.
Glycogen
  • Muscle glycogen:
    • Forms 2% of the weight of muscle.
    • Supplies glucose within muscles during contraction.
    • Muscle glycogen is only depleted after prolonged exercise.
  • Liver glycogen:
    • Forms 8-10% of the weight of the liver.
    • Maintains blood glucose.
    • Liver glycogen is depleted after 12-18 hours fasting.
Types of Glycogen Storage Diseases

  • Type I: Von Gierke’s Disease

    • Enzyme Deficiency: Glucose-6-Phosphatase
    • Affects liver and kidney.
    • Symptoms:
      • Severe fasting hypoglycemia.
      • Fatty liver, hepato- and renomegaly.
      • Progressive renal disease.
      • Growth retardation and delayed puberty.
      • Hyperlactic acidemia, hyperlipidemia, and hyperuricemia.
      • Normal glycogen structure; increased glycogen stored.

  • Type Ib: Glucose 6-Phosphate Translocase Deficiency

    • Characterized by neutropenia and recurrent infections.

  • Type II: Pompe’s disease

    • Enzyme Deficiency: Lysosomal α-1,4-Glucosidase (Acid maltase)
    • Lysosomal storage disease.
    • Generalized (primarily heart, liver, muscle).
    • Excessive glycogen concentrations found in abnormal vacuoles in the lysosomes.
    • Normal blood sugar levels.
    • Massive cardiomegaly.
    • Enzyme replacement therapy available.
    • Infantile form: early death typically from heart failure.
    • Normal glycogen structure.

  • Type III: Cori’s disease

    • Enzyme Deficiency: Amylo-1,6-glucosidase (Debranching Enzyme)
    • Deficiency of Glycogen Debranching Enzyme causes storage of glycogen with an abnormally compact structure, known as phosphorylase limit dextrin.
    • Glycogen structure is abnormal with four or one glucosyl residues at branch points.
    • Symptoms include low blood sugar, swollen abdomen due to an enlarged liver, excess amounts of fats, growth delay during childhood, and possible muscle weakness.

  • Type V: McArdle’s disease

    • Enzyme Deficiency: Glycogen phosphorylase (Muscle Glycogen Phosphorylase)
    • Skeletal muscle affected; liver enzyme normal.
    • Temporary weakness and cramping of skeletal muscle after exercise.
    • No rise in blood lactate during strenuous exercise.
    • Normal mental development.
    • Myoglobinemia and myoglobinuria.
    • Relatively benign, chronic condition.
    • High level of glycogen with normal structure in muscle.
    • Muscle cells rely on oxidation of fatty acids during rest; more demanding activity requires that they draw on their glycogen stockpile.

Fructose Metabolism Disorders

  • Major source of fructose is the disaccharide sucrose.
  • Also found as a free monosaccharide in many fruits, in honey, and in high-fructose corn syrup.
  • Deficiency of enzymes that metabolize fructose:
Fructose 1-phosphate aldolase (aldolase B) deficiency
  • Autosomal recessive.
  • Accumulation of fructose 1-phosphate in tissue.
  • Clinical Manifestations: hypoglycemia, nausea and vomiting, liver damage and jaundice, proximal renal tubular acidosis with urinary loss of phosphate and glucose, hyperuricemia
Fructokinase deficiency
Deficiency of fructose-1,6-biphosphatase

Galactosemia

  • Autosomal disorder caused by deficient or absent activities of one of the three enzymes involved in the galactose metabolic pathway:
    • Galactose-1-phosphate uridyl transferase deficiency
    • Galactokinase deficiency
    • Aldose reductase
  • GALACTOSE is found in dairy products, fruits, and vegetables. Major source of galactose is lactose obtained from milk.
Classic Galactosemia
  • Galactose 1-phosphate uridyltransferase (GALT) deficiency.
  • Autosomal recessive disorder (1:30,000 births).
  • Causes galactosemia and galactosuria, vomiting, diarrhea, and jaundice.
  • Accumulation of galactose 1-phosphate and galactitol in nerve, lens, liver, and kidney tissue causes liver damage, severe mental retardation, and cataracts.
  • Prenatal diagnosis is possible by chorionic villus sampling. Newborn screening is available.
Galactokinase Deficiency
  • Rare autosomal recessive disorder
  • Causes elevation of galactose in blood (galactosemia) and urine (galactosuria)
  • Causes galactitol accumulation if galactose is present in the diet.
  • Despite adequate treatment, at risk for developmental delays and, in females, premature ovarian failure.
Aldose Reductase
  • The enzyme is present in liver, kidney, retina, lens, nerve tissue, seminal vesicles, and ovaries.
  • It is physiologically unimportant in galactose metabolism unless galactose levels are high (as in galactosemia).
  • Elevated galactitol can cause cataracts.

Diabetes Mellitus

  • Is actually a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
Type 1 Diabetes
  • Juvenile, insulin-dependent (IDDM).
  • Is characterized by inappropriate hyperglycemia primarily a result of pancreatic islet B-cell destruction and a tendency to ketoacidosis.
  • Type 1 constitutes only 10% to 20% of all cases of diabetes and commonly occurs in childhood and adolescence.
  • This diabetic type is genetically related.
  • This disease is usually initiated by an environmental factor or infection (usually a virus) in individuals with a genetic predisposition and causes the immune destruction of the B-cells of the pancreas and, therefore, a decreased production of insulin.
  • Characteristics of type 1 diabetes include abrupt onset, insulin dependence, and ketosis.
  • Classic signs and symptoms include: polydipsia (excessive thirst) polyphagia (increased food intake) polyuria (excessive urine production)
  • These result in rapid weight loss, bouts of hyperventilation, mental confusion, and possible loss of consciousness (due to increased glucose to the brain).
Type 2 Diabetes
  • Adult-onset, non–insulin-dependent (NIDDM).
  • Is characterized by hyperglycemia as a result of an individual’s resistance to insulin or an insulin secretory defect.
  • Type 2 constitutes the majority (>80%) of the diabetes cases. Most patients in this type are obese or have an increased percentage of body fat distribution in the abdominal region.
  • Characteristics usually include adult onset of the disease and milder symptoms than in type 1, with ketoacidosis seldom occurring.
  • This type of diabetes often goes undiagnosed for many years and is associated with a strong genetic predisposition, with patients at increased risk with an increase in age, obesity, and lack of physical exercise.
  • These patients are more likely to go into a hyperosmolar coma and are at an increased risk of developing vascular complications.
General Diabetes Symptoms
  • In both type 1 and type 2 diabetes, the individual will be hyperglycemic, which can be severe.
  • Glucosuria can also occur after the renal tubular transporter system for glucose becomes saturated. This happens when the glucose concentration of plasma exceeds roughly 160-180 mg/dL in an individual with normal renal function and urine output.
  • As hepatic glucose overproduction continues, the plasma glucose concentration reaches a plateau around 300 to 500 mg/dL (17 to 28 mmol/L).