Urinary Sulfur Compounds in Down Syndrome

We have proposed that hydrogen sulfide contributes to the phenotypes of trisomy 21 (Down syndrome) (1). The cystathionine β-synthase (CBS; EC 4.2.1.22) gene is located on chromosome 21 (21q22.3). CBS is one of only three enzymes in mammals able to produce hydrogen sulfide in vitro (2)(3). Hydrogen sulfide is oxidized to thiosulfate (4), the precursor of sulfite and sulfate anions (5). CBS is overexpressed in fibroblasts of Down syndrome patients (6) at amounts ∼150% higher than in non-Down syndrome individuals. The expression of this gene is even higher in the myeloblasts of Down syndrome patients with leukemia: 12-fold higher than in non-Down syndrome individuals (7). We compared the urinary excretion of sulfur compounds in Down syndrome patients and controls to investigate the prediction that overexpression of CBS increases the production of hydrogen sulfide in these patients. Urinary thiosulfate was determined with the method of Voroteliak et al. (8). We measured urine concentrations of inorganic sulfate by turbidimetry (9), cystine and taurine by automated ion-exchange chromatography with ninhydrin detection (Jeol Amino Acid Analyzer), and creatinine by a manual Jaffe method. We studied 17 Down syndrome patients (12 males and 5 females; mean age, 21.6 ± 2.6 years) along with one relative of each patient (a parent or, in some cases, a sibling) as controls. The Down syndrome patients and their relatives received identical diets on the day before urine collection. Informed consent was obtained from Down syndrome patients and their relatives in accordance with the current revision of the Helsinki Declaration of 1975. The first urine produced in the morning was collected in a vial containing 270 mg of boric acid as a preservative. Sulfur compounds were excluded from the treatment of patients and controls.