Inherited Metabolic Disorders of Carbohydrate Metabolism Dr Essam

Inherited Metabolic Disorders of Carbohydrate Metabolism Dr. Essam H. Jiffri 1

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. 2

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Features of Glycogen Storage Diseases 4

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. 5

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. 6

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). 7

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. 8

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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. 10

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. 11

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. 12

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 mmol. L 1) Why was the OGTT performed ? 2) What do the results indicate ? 3) What is the most likely abnormality ? 13

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 Co 2 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 Co 2 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 14 diagnosis ?