Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester.

Tryptophan ethyl ester, a lipid-soluble tryptophan derivative, was used to bypass defective gastrointestinal neutral amino acid transport in a child with Hartnup disease. The child's baseline tryptophan concentrations in serum (20 +/- 6 microM) and cerebrospinal fluid (1.0 +/- 0.2 microM) were persistently less than 50% of normal values. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, was also less than 50% of normal (21 +/- 2 ng/ml). Serum tryptophan concentrations increased only modestly and briefly after an oral challenge with 200 mg/kg of oral L-tryptophan, reflecting the absorptive defect. An oral challenge with 200 mg/kg of tryptophan ethyl ester resulted in a prompt increase in serum tryptophan to a peak of 555 microM. Sustained treatment with 20 mg/kg q6h resulted in normalization of serum (66 +/- 15 microM) and cerebrospinal fluid tryptophan concentrations (mean = 2.3 microM). Cerebrospinal fluid 5-HIAA increased to more normal concentrations (mean = 33 ng/ml). No toxicity was observed over an 8-mo period of treatment, chronic diarrhea resolved, and body weight, which had remained unchanged for 7 mo before ester therapy, increased by approximately 26%. We concluded that tryptophan ethyl ester is effective at circumventing defective gastrointestinal neutral amino acid transport and may be useful in the treatment of Hartnup disease.
AuthorsA J Jonas, I J Butler
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 84 Issue 1 Pg. 200-4 (Jul 1989) ISSN: 0021-9738 [Print] UNITED STATES
PMID2472426 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Amino Acids
  • Niacinamide
  • Serotonin
  • Hydroxyindoleacetic Acid
  • tryptophan ethyl ester
  • Tryptophan
  • Amino Acids (blood, metabolism)
  • Animals
  • Biological Transport
  • Child, Preschool
  • Female
  • Hartnup Disease (drug therapy, metabolism)
  • Humans
  • Hydrolysis
  • Hydroxyindoleacetic Acid (cerebrospinal fluid)
  • Male
  • Niacinamide (therapeutic use)
  • Rats
  • Rats, Inbred Strains
  • Serotonin (cerebrospinal fluid)
  • Tryptophan (analogs & derivatives, blood, cerebrospinal fluid, therapeutic use)

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