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Clinical Chemistry 47: 1500-1501, 2001;
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(Clinical Chemistry. 2001;47:1500-1501.)
© 2001 American Association for Clinical Chemistry, Inc.

Letters

Urinary Sulfur Compounds in Down Syndrome

Maria-Cristina Belardinelli1, Allel Chabli1, Bernadette Chadefaux-Vekemans1 and Pierre Kamoun1a

1 Laboratoire de Biochimie Médicale B, UMR CNRS 8602, Hôpital Necker Enfants Malades, 149, Rue de Sèvres, 75743 Paris cedex 15, France

aAddress correspondence to this author at: Biochimie B, Tour Lavoisier, 75743 Paris cedex 15, France. Fax 33-1-44-49-51-30; e-mail pierre.kamoun{at}nck.ap-hop-paris.fr.


To the Editor:

We have proposed that hydrogen sulfide contributes to the phenotypes of trisomy 21 (Down syndrome) (1). The cystathionine ß-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.

A significant difference in urinary excretion of thiosulfate was observed between patients and controls (Table 1 ). Cystine, taurine, and inorganic sulfate excretions were similar for Down syndrome patients and controls. Our control data for urinary thiosulfate excretion are comparable to previous reports that used an assay based on chromatographic separation with fluorescence detection of bromobimane derivatives (4).


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  		Table 1. Urinary excretion of sulfur compounds.1

Our results indicate that there is an overproduction of hydrogen sulfide in Down syndrome, thiosulfate being the main catabolite of hydrogen sulfide. Additional studies are needed to determine its possible toxic effect in Down syndrome patients.


References

  1. Kamoun P. Mental retardation in Down’s syndrome: a hydrogen sulfide hypothesis. Med Hypotheses 2001;in press..
  2. Stipanuck MH, Beck PW. Characterization of the enzymatic capacity for cysteine desulphydration in liver and kidney of the rat. Biochem J 1982;206:267-277.[ISI][Medline] [Order article via Infotrieve]
  3. Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 1996;16:1066-1071.[Abstract/Free Full Text]
  4. Kangas J, Savolainen H. Urinary thiosulphate as an indicator of exposure to hydrogen sulphide vapour. Clin Chim Acta 1987;164:7-10.[ISI][Medline] [Order article via Infotrieve]
  5. Huang J, Khan S, O’Brien PJ. The glutathione dependence of inorganic sulfate formation from L or D cysteine in isolated rat hepatocytes. Chem-Biol Interact 1998;110:189-202.[ISI][Medline] [Order article via Infotrieve]
  6. Chadefaux B, Rethore MO, Raoul O, Ceballos I, Poissonnier M, Gilgenkranz S, Allard D. Cystathionine ß synthase: gene dosage effect in trisomy 21. Biochem Biophys Res Commun 1985;128:40-44.[ISI][Medline] [Order article via Infotrieve]
  7. Taub JW, Huang X, Matherly LH, Stout ML, Buck SA, Massey GU, et al. Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and Daunorubicin. Blood 1999;94:1393-1400.[Abstract/Free Full Text]
  8. Voroteliak V, Cowley DM, Florin THJ. Improved colorimetric determination of urinary thiosulfate to study intermediate sulfur metabolism in humans. Clin Chem 1993;39:2533-2534.[ISI][Medline] [Order article via Infotrieve]
  9. Lundquist P, Martensson J, Sorbo B, Ohman S. Turbidimetry of inorganic sulfate, ester sulfate and total sulfur in urine. Clin Chem 1980;26:1178-1181.[Abstract/Free Full Text]




This Article
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Right arrow Articles by Belardinelli, M.-C.
Right arrow Articles by Kamoun, P.
Related Collections
Right arrow Molecular Diagnostics and Genetics

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