Hypoglycemia Leucine

Inherited defects in the enzymes of (3-oxidation and ketogenesis also lead to nonketotic hypoglycemia, coma, and fatty hver. Defects are known in long- and short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the long-chain enzyme may be a cause of acute fetty liver of pr nancy). 3-Ketoacyl-CoA thiolase and HMG-CoA lyase deficiency also affect the degradation of leucine, a ketogenic amino acid (Chapter 30). 

Nutritional therapy for HMG-CoA lyase deficiency has two major goals. First, the prescribed diet aims to provide enough total protein and calories to achieve normal growth and maintain metabolic balance in the context of a leucine-restricted diet. Equally important, the nutritional therapy focuses on preventing excess catabolism, acidosis, and hypoglycemia, especially during times of acute illness. For these patients, it is particularly important to avoid fasting at any time. 

In summary, HMG-CoA lyase deficiency is a unique inborn error of metabolism with profound effects on both amino acid catabolism and metabolic homeostasis in the fasted state. Management of these patients is difficult and requires constant attention to daily nutrition and timely intervention during acute illness. Fortunately, nutritional therapy treatment that provides a diet adequate for growth but with limited intake of leucine and prevents fasting and hypoglycemia enables individuals with HMG-CoA lyase deficiency to live normal active lives. 

Zammarchi E, Filippi L, Noverabre E, Donati MA. Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia. Metabol Clin Exp 1996 45 957-60. 

Leucine induces hypoglycemia and a rise in im-munologically active insulin by a mechanism that is still unknown. Whether other amino acids exhibit similar properties is not certain. 

The pathogenesis of many of these hypoglycemic conditions has been discussed in other chapters of this book. Only the special cases— pancreatic and nonpan-creatic tumors, leucine initiation of hypoglycemia, and some hypoglycemic agents—will be considered here. 

Administration of leucine to adults or young children has no or little effect on insulin release, but in some children leucine injection causes hypoglycemia and increased levels of circulating insulin. 

These patients have convulsions at an early age, abnormal EEG patterns, and glucose levels of 30 and 31mg/100ml after oral administration of leucine. Daily administration of diazoxide may satisfactorily control the hypoglycemia. 

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