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.