The origin of halitosis in cystinotic patients due to cysteamine treatment

Mol Genet Metab. 2007 Jul;91(3):228-33. doi: 10.1016/j.ymgme.2007.04.002. Epub 2007 May 21.

Abstract

Introduction: Cystinosis is a rare autosomal recessive disorder characterized by the intralysosomal accumulation of cystine. Cysteamine removes cystine from the lysosome and slows down the progression of the disease. One of its side effects is the induction of halitosis, which can interfere with patients' willingness to comply with cysteamine treatment.

Objective: To identify breath sulphur compounds causing halitosis induced by cysteamine therapy in patients with cystinosis.

Study design: After the ingestion of 15mg/kg cysteamine whole blood (n=4), urine (n=4) and breath (n=8) volatile sulphur compounds levels were measured every 60min over a 360min period by gas chromatography and the cysteamine plasma concentrations (n=4) were measured by high-performance liquid chromatography.

Results: The expired air of cystinotic patients contained elevated concentrations of methanethiol (MT, median maximum value 0.5 (range 0-11)nmol/L) and, in particular, dimethylsulphide (DMS, median maximum value 15 (range 2-83)nmol/L). DMS concentrations higher than 0.65nmol/L are known to cause halitosis. Maximal plasma values of cysteamine (median 46 (range 30-52)micromol/L) preceded those of MT and DMS, confirming that cysteamine is converted to MT and DMS. Less than 3% of the amount of cysteamine ingested was excreted as MT and DMS via expired air and 0.002% via urine.

Conclusion: Halitosis induced by cysteamine intake is caused by DMS and to a lesser extent by MT, excreted via the expired air. Further studies should focus on the possibilities of reducing the formation of these volatile sulphur compounds or masking their odour, which would improve the rates of compliance with cysteamine treatment.

MeSH terms

  • Adolescent
  • Adult
  • Breath Tests
  • Child
  • Cysteamine / adverse effects*
  • Cysteamine / pharmacokinetics
  • Cysteamine / therapeutic use
  • Cystinosis / drug therapy*
  • Female
  • Halitosis / chemically induced*
  • Humans
  • Male
  • Sulfhydryl Compounds / blood
  • Sulfhydryl Compounds / urine
  • Sulfides / blood
  • Sulfides / urine

Substances

  • Sulfhydryl Compounds
  • Sulfides
  • methylmercaptan
  • Cysteamine
  • dimethyl sulfide