HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Levtchenko, E. Articles by Blom, H. Search for Related Content PubMed PubMed Citation Articles by Levtchenko, E. Articles by Blom, H. Related Collections Molecular Diagnostics and Genetics Drug Monitoring and Toxicology Endocrinology and Metabolism

Comparison of Cystine Determination in Mixed Leukocytes vs Polymorphonuclear Leukocytes for Diagnosis of Cystinosis and Monitoring of Cysteamine Therapy

¹ Department of Paediatric Nephrology and² Laboratory of Paediatrics and Neurology, University Medical Centre St Radboud, Nijmegen, The Netherlands;

^aaddress correspondence to this author at: Department of Paediatric Nephrology, UMC St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands; fax 31-24-361-9348, e-mail e.levtchenko@cukz.umcn.nl

The first 20% of the full text of this article appears below.

Cystinosis is a rare autosomal recessive disorder caused by mutations of cystinosis gene (CTNS; chromosome 17p13), which encodes the lysosomal cystine carrier. The continuous accumulation of cystine in the lysosomes leads to intracellular crystal formation throughout the body. Patients with the common infantile form of cystinosis develop renal Fanconi syndrome 3–6 months after birth and end-stage renal failure before the age of 10 years. Treatment with the aminothiol cysteamine depletes intralysosomal cystine via a disulfide exchange reaction with formation of cysteine-cysteamine mixed-disulfides and cysteine; these exit the lysosomes via lysosomal carriers for lysine and cysteine, respectively (1). When started at an early age, cysteamine treatment prevents or postpones the deterioration of renal function and the occurrence of extrarenal complications such as hypothyroidism, diabetes mellitus, retinopathy, encephalopathy, and myopathy (1).

Accurate measurement of intracellular cystine content is obligatory for the diagnosis of cystinosis as well as for the monitoring of treatment with cysteamine. Historically, cystine has been measured in mixed leukocyte (ML) preparations, despite the fact that it preferentially accumulates in polymorphonuclear leukocytes (PMN) and monocytes (2). We therefore compared intracellular cystine content in ML preparations and in PMN cells of healthy controls, obligate heterozygotes, and patients at diagnosis and under cysteamine therapy. Because the isolation of PMN may pose practical problems in some laboratories, we also investigated whether preservation of whole blood at room temperature influenced intracellular cystine content. If the cystine concentration remains constant, it would allow the shipping of whole-blood samples.

MLs were isolated exactly as described by de Graaf-Hess et al. (3). All solutions were kept at 4 °C. PMN cells were isolated from 10 mL of blood by addition of 2 . . . [Full Text of this Article]

The following articles in journals at HighWire Press have cited this article:

				E. Levtchenko, A. de Graaf-Hess, M. Wilmer, L. van den Heuvel, L. Monnens, and H. Blom Altered status of glutathione and its metabolites in cystinotic cells Nephrol. Dial. Transplant., September 1, 2005; 20(9): 1828 - 1832. [Abstract] [Full Text] [PDF]