Infantile Hypoglycaemia due to Inherited Deficiency of Glycogen Synthetase in Liver

In 1909 Garrod introduced the concept of the metabolic block.Over 70 diseases are now thought to be due to inborn errors of metabolism, and of these some 20 have been shown to be due to a single enzyme defect.We now report the clinical con- dition resulting from the congenital absence of the liver enzyme glycogen synthetase.Our report is based on the study of identical twins who become hypoglycaemic after an overnight fast.Hypoglycaemia is a feature of cretinism, hypo- pituitarism, adrenal insufficiency, galactosaemia, hereditary fructose intolerance, severe liver disease, glycogen storage disease and islet cell adenoma or hyperplasia.In many hypoglycaemic infants, how- ever, no cause has been found.McQuarrie (1954) reporting on a large series of these cases proposed the term 'idiopathic spontaneous hypoglycaemia'.Cochrane, Payne, Simpkiss and Woolf (1956) described patients in whom hypoglycaemia developed after protein meals, and after the administration of L-leucine.More recently Mabry, DiGeorge and Auerbach (1960) have shown that L-leucine is probably the only amino acid with this action.Broberger and Zetterstr6m (1961) described a series of hypoglycaemic infants who did not increase adrenaline secretion in response to hypoglycaemia.Our investigations show that the twins to be described have a reduced capacity for the storage of glycogen in the liver.In a liver biopsy sample from one twin, complete absence of glycogen synthetase activity has been demonstrated.