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Horm Metab Res 2006; 38(10): 678-682
DOI: 10.1055/s-2006-954584
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Vaso-occlusion in Schimke-immuno-osseous Dysplasia: Is the NO Pathway Involved?

T. Lücke 1 , D. Tsikas 2 , N. K. Kanzelmeyer 1 , C. F. Boerkoel 3 , J. M. Clewing 3 , B. Vaske 4 , J. H. H. Ehrich 1 , A. M. Das 1
  • 1Department of Pediatrics, Hanover Medical School, Hanover, Germany
  • 2Institute of Clinical Pharmacology, Hanover Medical School, Hanover, Germany
  • 3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  • 4Biometric Institute, Hanover Medical School, Hanover, Germany
Further Information

Publication History

Received 26 January 2006

Accepted after revision 6 June 2006

Publication Date:
30 October 2006 (online)

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Abstract

Schimke-immuno-osseous dysplasia (SIOD) is an autosomal recessive disorder with the main clinical findings of spondyloepiphyseal dysplasia, nephrotic syndrome, and defective cellular immunity. Vaso-occlusive processes, especially generalized atherosclerosis, are a life-limiting complication in patients with severe SIOD. The nitric oxide synthase (NOS) oxidizes L-arginine to nitric oxide (NO). NO is a potent vasodilator with inhibitory effects on platelet aggregation and the development of atherosclerosis. We hypothesized that reduced NO production due to antagonism of NOS by asymmetric dimethylarginine (ADMA) would be a possible pathophysiological mechanism for vaso-occlusion in SIOD. We tested this hypothesis in 10 patients with SIOD and 10 age-matched healthy controls. Plasma and urine levels of nitrite and nitrate, the indicators of NO synthesis, and of ADMA, an endogenous NOS inhibitor, in children suffering from SIOD were not significantly different from those in the age-matched healthy controls. Our results suggest that the L-arginine/NO pathway is not altered in SIOD. Antagonism of NOS by ADMA does not seem to be the cause of premature general atherosclerosis in SIOD. The underlying pathology of vaso-occlusion in SIOD still remains unclear.

Key words

Atherosclerosis - vascular dysfunction - vaso-occlusive disease - asymmetric dimethylarginine - nitrite - nitrate - mass spectrometry

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Correspondence

Thomas Lücke

Department of Pediatrics

Carl-Neuberg Str. 1

30623 Hanover

Phone: +49/511/53 23 22 0

Fax: +49/511/53 28 07 3

Email: luecke.thomas@mh-hannover.de

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