Inherited Metabolic Disorders of Carbohydrate Metabolism

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Inherited Metabolic Disorders of Carbohydrate
Metabolism

• Dr. Essam H. Jiffri

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Glycogen Storage Diseases (Glycogenoses)

• -Glycogen storage diseases are a group of
  inherited conditions characterized by
• tissue deposits of glycogen that are abnormal
  in amount or structure.
• -Glycogen is found principally in liver and
  muscle, and is synthesized from glucose
• by different enzymes from those which mediate
  glycogenolysis.

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Features of Glycogen Storage Diseases
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Features of Glycogen Storage Diseases

• -Type I glycogenosis (von Gierke's disease) is
  caused by a deficiency in glucose-6-phosphatase,
  which results in impaired glucose release from,
  glycogen and thus hypoglycaemia.

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Features of Glycogen Storage Diseases

• -Lactate metabolism is also impaired as it is
  converted to glucose via glucose-6-phosphate in
  the Cori cycle, metabolic acidosis is a clinical
  feature.

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Features of Glycogen Storage Diseases

• -Hyperuricaemia is also seen, partly due to
  increased metabolism of glucose-6-phosphate via
  the pentose phosphate pathway, forming
  ribose-5-phosphate and purines (the catabolism
  of purines occurs through a common pathway
  leading to uric acid formation).

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Features of Glycogen Storage Diseases

• -In glycogen synthase deficiency, which is
  extremely rare, very little glucose is converted
  to glycogen, although conversion to lactate does
  occur, with
• hyperglycaemia and hyperlactataemia being
  features of this deficiency.

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Disorders of Galactose Metabolism

• Galactosaemia
• -Impaired metabolism of galactose may result from
  three enzyme defects.
• -The most common is galactose-l-phosphate uridyl
  transferase deficiency in which feeding
  difficulties, vomiting and hypoglycaemia occur
  soon after birth.

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Disorders of Fructose Metabolism

• Hereditary Fructose Intolerance
• -Hereditary fructose intolerance is due to a
  deficiency of fructose-1-phosphate aldolase B
  which converts fructose into two 3-carbon units,
  mainly in the liver.

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Disorders of Fructose Metabolism

• Hereditary Fructose Intolerance
• -Symptoms do not develop until sucrose is
  introduced into the diet, when hypoglycaemia and
  vomiting occur, probably as a result of
  intracellular
• accumulation of fructose-l-phosphate.

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Case Histories

• Case 1
• A 26-year-old patient expecting her second child
  was found to have glycosuria on routine testing
  of her urine in the antenatal clinic. An oral
  glucose tolerance test was carried out with the
  following results
• Fasting blood glucose 4.9 mmol/L
• (normal, 3.6-6.0 mmol/L)
• 1-h blood glucose 6.4 mmol/L
• 2-h blood glucose 5.2 mmolL
• 1) Why was the OGTT performed ?
• 2) What do the results indicate ?
• 3) What is the most likely abnormality ?

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• Case 2
• A 27-year-old patient with IDDM was admitted in a
  drowsy and confused state. The breath smelled of
  acetone and a history of a chest infection was
  obtained from a
• relative. Initial investigations showed
  the following
• Sodium 137 mrnol/L (normal, 137-144 mmol/L)
• Potassium 5.7 mmol/L (normal, 3.3-4.4
  mmol/L)
• Total Co2 11 mmol/L (normal, 24-31 mmol/L)
• Urea 11.4 mmol/L (normal, 3.1- 7.9 mmol/l)
• Blood glucose 23 mmol/L (normal, 3.6-6.0
  mmol/L)
• 1) What is the explanation for the low total Co2
  result ?
• 2) Why were the plasma potassium and urea levels
  increased ?
• 3) What is the most likely abnormality?
• 4) What other analyte may be measured to confirm
  diagnosis ?