1213 LOSS OF APPETITE IN UREA CYCLE DISORDERS (UCD): THERAPEUTIC APPROACHES

Abstract

Hyperammonemic animals have decreased food intake and increased serotonin (5-HT) and its metabolite 5-hydroxy indoleacetic acid (HIAA) in brain (Life Sci. 33: 2417, 1983). We have treated 2 anorectic children with UCD with precursor restriction and antiserotonergic drugs. A 7 yo. with argininosuccinic aciduria refused all oral feedings and had elevated levels of HIAA in CSF (78ng/ml). She responded to restriction of dietary tryptophan, Trp (7 vs. 34 mg/kg/d) with the onset of spontaneous food intake. She was then treated with the 5-HT receptor blocker cyproheptadine (Cyp), 0.3 mg/kg/d, while receiving 14 mg/kg/d Trp. Food intake during a 5 min. free feeding condition was increased under both of the low Trp conditions as compared to the high Trp condition. However, % of total daily calories consumed during free feeding, a measure of appetite, was higher in the low Trp + Cyp condition, 12.6 + 2.8%, than in the low Trp condition alone, 8.2 + 1.1%, p <.01 (df=ll) suggesting a synergistic effect of Trp restriction and Cyp. Pizotifen, another 5-HT receptor blocker reduced feeding time in a 7 mo. citrullinemic child from 180 to 130 min/d, p=.02 at a dose of 0.11 mg/kg/d and to 105 min/d at 0.17 mg/kg/d. Decreasing oral Trp from 29 to 15 mg/kg/d resulted in further improvement. In addition to good metabolic control, restriction of 5-HT precursors combined with antiserotonergic drugs may be useful in the treatment of appetite problems in UCD.