Abstract
Molybdenum cofactor deficiency (MoCD) is a rare inherited metabolic disorder characterized by severe and progressive neurological damage mainly caused by the loss of sulfite oxidase activity. Elevated urinary levels of sulfite, thiosulfate, and S-sulfocysteine (SSC) are hallmarks in the diagnosis of MoCD and sulfite oxidase deficiency (SOD). Recently, a first successful treatment of a human MoCD type A patient based on a substitution therapy with the molybdenum cofactor precursor cPMP has been reported, resulting in nearly complete normalization of MoCD biomarkers. Knowing the rapid progression of the disease symptoms in nontreated patients, an early diagnosis of MoCD as well as a sensitive method to monitor daily changes in SSC levels, a key marker of sulfite toxicity, is crucial for treatment outcome. Here, we describe a fast and sensitive method for the analysis of SSC in human urine samples using high performance liquid chromatography (HPLC). The analysis is based on precolumn derivatization with O-phthaldialdehyde (OPA) and separation on a C18 reverse phase column coupled to UV detection. The method was extended to human serum analysis and no interference with endogenous amino acids was found. Finally, SSC values from 45 pediatric urine, 75 adult urine, and 24 serum samples from control individuals as well as MoCD patients are reported. Our method represents a cost-effective technique for routine diagnosis of MoCD and SOD, and can be used also to monitor treatment efficiency in those sulfite toxicity disorders on a daily basis.
Competing interests: None declared.
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Abbreviations
- HPLC:
-
High performance liquid chromatography
- MoCD:
-
Molybdenum cofactor deficiency
- Moco:
-
Molybdenum cofactor
- OPA:
-
O-phthaldialdehyde
- SOD:
-
Sulfite oxidase deficiency
- SSC:
-
S-sulfocysteine
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Acknowledgments
We thank Parmanand Arjune, MD, PhD (Cologne, Germany) for providing a large number of urine and serum samples. We are grateful to James Pitt, PhD (Melbourne, Australia) for the comparative analysis of selected urine samples. We gratefully acknowledge Bernd Schwahn, MD, Steve Bowhay, PhD, Peter G. Galloway, MD (Royal Hospital for Sick Children, Glasgow, Scotland), Julia Hennemann, MD (Pediatric Unit, Charité Berlin, Germany), Francjan J. van Spronsen, MD, PhD (University Medical Center, Groningen, Netherlands), and Illona Weis, MD (Pediatric Unit, Gemeinschaftsklinikum Koblenz-Mayen, Germany) and other colleagues for providing urine samples of patients.
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Communicated by: Verena Peters.
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Belaidi, A.A., Arjune, S., Santamaria-Araujo, J.A., Sass, J.O., Schwarz, G. (2011). Molybdenum Cofactor Deficiency: A New HPLC Method for Fast Quantification of S-Sulfocysteine in Urine and Serum. In: JIMD Reports - Case and Research Reports, 2012/2. JIMD Reports, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_89
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