Anorexia and food refusal are problems frequently encountered in the clinical management of children with inborn errors of metabolism. They are also common complaints associated with certain medications. It is suggested that an alteration in central nervous system serotonin metabolism or receptor activation may be a significant influence on feeding behavior in children with metabolic disorders associated with elevated ammonium levels. Preliminary studies in this laboratory have shown elevated levels of cerebrospinal hydroxy indoleacetic acid in an anorectic child with argininosuccinic aciduria. Decreasing the intake of tryptophan led to improved feeding associated with a decrease in the level of hydroxy indoleacetic acid. To investigate this hypothesis, feeding disorders in children with inborn errors of urea synthesis, and in epileptic patients receiving the anticonvulsant valproate which induces hyperammonemia will be studied. Levels of biogenic amines in cerebrospinal fluid of these patients will be measured and alterations in serotonin metabolism will be treated by manipulating dietary tryptophan and by using medications that affect serotonin metabolism. Effects of elevated ammonium levels on feeding behavior and serotonin metabolism will also be studied in three animal models associated with hyperammonemia: urease infused rats, valproate treated rats, and sparse fur mice. Attempts to modify feeding abnormalities will include altering tryptophan intake and administering drugs that affect serotonin metabolism. This study should add to knowledge about the biological basis of feeding disturbances in certain disorders and provide new treatment approaches to these conditions.
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