Transcript CLINICAL CHEMIISTRY (MT 305) CARBOHYDRATE LECTURE ONE

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 1
Case Histories
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
Potassium
Total Co2
Urea
Blood glucose
137 mrnol/L (normal, 137-144 mmol/L)
5.7 mmol/L (normal, 3.3-4.4 mmol/L)
11 mmol/L (normal, 24-31 mmol/L)
11.4 mmol/L (normal, 3.1- 7.9 mmol/l)
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 ?
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