[Metabolic changes in aromatic amino acids and monoamines in infantile autism and development of new treatment related to the finding].
A new method for measurement of the turnover rate of aromatic amino acids and related compounds in vivo using stable isotopes was developed. Deuterium-and carbon 13-labeled phenylalanine and deuterium-labeled tryptophan were used as tracers. This method was applied for the analysis of amino acid and amine metabolism in infantile autism. Marked disturbances of uptake of deuterated phenylalanine and tryptophan from intestine into blood were found in a portion of autistic patients (group A). In another group of the patients a remarkable decrease of turnover of tyrosine in blood was found (group B). This phenomenon was confirmed by an experiment using carbon 13 labeled phenylalanine. These findings might suggest that supply of tyrosine and free tryptophan to the brain (in group A) or supply of tyrosine (group B) to the brain might be decreased. We postulated that in some of autistic patients there might exist decreases in synthesis of catecholamine or serotonin. Based on the hypothesis, we started a new treatment with L-DOPA and 5 HTP in small doses, and found significant effects in some patients. However, in some, the amino acids caused marked aggravation of the symptoms. Recently, Hayaishi and his colleagues reported that R-tetrahydrobiopterin (R-THBP) could enhance biosynthesis of catecholamine and serotonin in the brain. Therefore, we started a clinical trial concerning effects of R-THBP. In the beginning, 17 cases were treated and patients younger than 5 years old showed marked improvement. Then, a double blind trial with inactive placebo was performed.(ABSTRACT TRUNCATED AT 250 WORDS)
Naruse
H
H
Hayashi
T
T
Takesada
M
M
Nakane
A
A
Yamazaki
K
K
D006916:5-Hydroxytryptophan / Q000627:therapeutic use*; D000596:Amino Acids / Q000378:metabolism*; D001321:Autistic Disorder / Q000188:drug therapy / Q000378:metabolism*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002247:Carbon Isotopes; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003903:Deuterium; D004311:Double-Blind Method; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D010649:Phenylalanine / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D000596:Amino Acids; D015306:Biogenic Monoamines; D002247:Carbon Isotopes; D001708:Biopterins; D007980:Levodopa; D010649:Phenylalanine; D014364:Tryptophan; D003903:Deuterium; D006916:5-Hydroxytryptophan; C003402:sapropterin