Abstract

Genetics in Medicine (1999) 1, 42–42; doi:10.1097/00125817-199901000-00014

Autism associated with elevated glutamine and glycine levels and clinical response to dextromethorphan

R Hamid1, S McGrew1 and J A Phillips III1

1Dept. Peds, Vanderbilit Univ. Schl of Medicine, Nashville, TN.

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Abstract

Autism is a pervasive developmental disorder characterized by social relating and communicating impairments and restricted, repetitive or stereotypical behavior with onset by 3 years of age. A genetic etiology is suggested by developmental anomalies; increased risks for sibs and concordance for monozygotic twins. In screening a series of consecutive autistic probands, we detected 2/60 who had elevated plasma levels of glutamine (Glu) and glycine (Gly). The first was diagnosed as having autism at 2 10/12. His Glu (mean 884-normal 370-682) and Gly (mean 379-normal 120-315) levels were consistently elevated on all 5 studies done between 4 11/12 and 6 years of age. His Phe (mean 86-normal 39-78) and Ser (mean 185-normal 31-131) levels were usually elevated. Urine Glu, Gly, Phe and Ser levels were 1410 (165-510), 5663 (569-1395), 134 (27-51) and 1163 (148-360). His CSF Glu was 708 (normal 356-680) while his Gly, Phe and Ser levels were normal. His electrolytes, anion gap and plasma ammonia levels were all well within the normal range and his urine organic acid profile was normal. To competitively block his elevated Glu and Gly levels he was empirically treated with dextromethorphan (DM) at 5 mgm/kg/day (Delsym) divided BID. His special education and classroom teachers and both speech and occupational therapists (blinded to treatment) noted significant improvement in his expressive and receptive language skills, attention span and focus; motor planning and socialization with peers. After withdrawal of DM regression in all improved areas was noted by all of these treatment blinded observers. He continues to respond to resumed, long term DM treatment. Our data suggest some autistic children have consistent elevations of Glu and Gly and they may respond clinically to DM. Further studies are needed to determine the cause of these biochemical findings and the responce of other subjects to DM or other competitive inhibitors.