Homocystinuria due to cystathionine synthase deficiency. Studies of nitrogen balance and sulfur excretion.

A C T Apparent nitrogen balances and urinary sulfur excretions were determined for normal subjects, seven cystathionine synthase-deficient patients, and a single cystathioninuric patient on semisynthetic diets containing low-adequate amounts of methionine and very low amounts (12 mg daily, or less) of cystine.The amounts of supplemental cystine required to prevent abnormally high nitrogen or sulfur losses were deter- mined.The five cystathionine synthase-deficient patients who had low residual activities of this enzyme detected in fibroblast and/or liver extracts did not lose more nitrogen or sulfur on diets virtually devoid of cystine than did the normal subjects.These results suggest that the widely expressed opinion that cystine is an essential amino acid for cystathionine synthase-deficient patients requires modification.Residual enzyme activity of only a few percent of normal may obviate such a cystine requirement.These results are compatible with, and lend support to, the working hypothesis which states that the pyridoxine response in cystathionine synthase-deficient patients is mediated by an increase in the residual activity of the affected enzyme.* Personal communication from Dr. A. Sass-Kortasak.Patient previously reported (20). 1 Personal communication from Dr. N. Holtzmann.§ Personal communication from Dr. V. McKusick. 1 1 Patient's urinary and plasma homocystine and methionine values remained essentially unchanged despite the ad- ministration of 500 mg pyridoxine -HCl daily for 11 days.Serum folate was normal.¶ Previously unpublished specific activities of cystathionine synthase, assayed in fibroblast extracts without addition of pyridoxal phosphate, or in the presence of pyridoxal phosphate added at final concentrations of 0.1, 1.0, and 5.0 mM were as follows: Ca.Me., 0.46, 0.64, 0.83, 0.73; Fr.Mi., 0.59, 0.70, 0.96, 0.65 (mean of two assays); Vi.Sw. 0, 0, 0, 0 (i.e., <0.10).Activities are in nmol cystathionine/mg protein/135 min; control mean, 31.7;range, 3.7-60.0(18).** Personal communication from Dr. G. Morrow, III.Morrow's observation was confirmed during the present studies.Hypermethioninemia, homocystinemia, hypocystinemia, and homocystinuria all remained relatively constant during 10 days of treatment with a daily oral dose of 500 mg pyridoxine-HCl.1034