A Sterol Panel for Rare Lipid Disorders: Sitosterolemia, Cerebrotendinous Xanthomatosis and Smith-Lemli-Opitz Syndrome.

Autor:	Westbye AB; Hormone Laboratory, Dept. Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway; Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway. Electronic address: alwest@ous-hf.no., Dizdarevic LL; Lipid Clinic, Oslo University Hospital, Aker, Oslo, Norway., Dahl SR; Hormone Laboratory, Dept. Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway; Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway., Asprusten EA; Lipid Clinic, Oslo University Hospital, Aker, Oslo, Norway., Bliksrud YT; Norwegian National Unit for Diagnostics of Congenital Metabolic Disorders, Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Norway; Metabolic Molecular Biology Research Group, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Sandblom AL; Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Diczfalusy U; Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden., Thorsby PM; Hormone Laboratory, Dept. Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway; Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Retterstøl K; Lipid Clinic, Oslo University Hospital, Aker, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Nov 18, pp. 100698. Date of Electronic Publication: 2024 Nov 18.
DOI:	10.1016/j.jlr.2024.100698
Abstrakt:	Background: Disease-specific sterols accumulate in the blood of patients with several rare lipid disorders. Biochemical measurement of these sterols is important for correct diagnosis and sometimes monitoring of treatment. Existing methods to measure sterols in blood, particularly plant sterols, are often laborious and time consuming. Partly as a result, clinical access to sterol measurements is limited in many parts of the world. Methods: A simple and rapid method to extract free sterols from human serum and quantitate their concentration using isotope-dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) without derivatization was developed. The method was designed to be "compatible" with routine workflows (e.g. 96-well format) in a clinical lab and extensively validated. Serum from at least 125 controls were analyzed and used to estimate the upper reference limits for sitosterol, campesterol, stigmasterol, desmosterol, 7-dehydrocholesterol (7DHC), lathosterol and cholestanol. Serum from patients with the rare lipid disorders sitosterolemia (n=7), Smith-Lemli-Optiz syndrome (SLOS; n=1) and cerebrotendinous xanthomatosis (CTX; n=1) were analyzed. Results: All seven sitosterolemia patients had greatly elevated levels of free plant sterols (sitosterol, campesterol and stigmasterol) compared to the controls. The SLOS serum contained massively increased concentrations of 7DHC. CTX serum contained greatly increased concentrations of cholestanol, as well as 7DHC and lathosterol. Spiking experiments indicated that the method is likely also useful for the diagnosis of desmosterolosis and lathosterolosis. Conclusion: The reported method is a relatively simple and fast LC-MS/MS method capable of quantitating diagnostically important sterols and differentiated patients with three rare lipid disorders from controls. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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