SEROTONIN AND ANOREXIA IN A PATIENT WITH ARGININOSUCCINASE (AL) DEFICIENCY

Abstract

We studied a 6 y.o. girl with AL deficiency who required NG feedings since 18 m.o. because of complete refusal to eat. NG Feedings contained 1g/kg protein (25g), including .75 g tryptophan (trp) and 1600 cal/d supplemented with arginine 4 mmol/kd/d. Weight was 10% and plasma ammonium was 40-60 uM (normal < 35). CSF 5-hydroxy-indolacetic acid (HIAA) was 91 ng/ml, normal < 35 and homovanillic acid (HVA) was 84 ng/ml, normal< 110. Behavior modification (BM) therapy led to a mean oral protein intake of 12 g/d throughout the study. However she ate no food during a 5 min. spontaneous intake (SI) period preceeding each BM meal. We reduced trp, the precursor of serotonin, from the NG feedings to .15 g/d; 5 days later, she began to eat during the SI period (2-18g prot/d). CSF HIAA level fell to 29 ng/ml, HVA was unchanged at 74 ng/ml. Trp was then increased to .55 g/d, and patient stopped SI eating in 2 days. Cyproheptadine (8 mg/d), a serotonin antagonist, did not affect HIAA level (102 ng/ml) or cause SI. REM sleep was markedly decreased (3% of total sleep) during high CSF HIAA and increased towards normal (11%) when trp-intake was decreased and HIAA fell. These results indicate a hyperserotonergic state in an anorectic child with AL deficiency. SI appeared when trp intake was decreased. This finding may have implications in other disorders associated with anorexia or hyperphagia.