A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome
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 labor...
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Elsevier
2025-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524002037 |
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| author | Alexander Bauer Westbye Lili L. Dizdarevic Sandra R. Dahl Emil Andreas Asprusten Yngve Thomas Bliksrud Anita Lövgren Sandblom Ulf Diczfalusy Per M. Thorsby Kjetil Retterstøl |
| author_facet | Alexander Bauer Westbye Lili L. Dizdarevic Sandra R. Dahl Emil Andreas Asprusten Yngve Thomas Bliksrud Anita Lövgren Sandblom Ulf Diczfalusy Per M. Thorsby Kjetil Retterstøl |
| author_sort | Alexander Bauer Westbye |
| collection | DOAJ |
| description | 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. 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-Opitz syndrome (SLOS; n = 1), and cerebrotendinous xanthomatosis (CTX; n = 1) were analyzed. 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. 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. |
| format | Article |
| id | doaj-art-1868dd5b90814578a1ff0b695f83a42e |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-1868dd5b90814578a1ff0b695f83a42e2025-01-30T05:12:35ZengElsevierJournal of Lipid Research0022-22752025-01-01661100698A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndromeAlexander Bauer Westbye0Lili L. Dizdarevic1Sandra R. Dahl2Emil Andreas Asprusten3Yngve Thomas Bliksrud4Anita Lövgren Sandblom5Ulf Diczfalusy6Per M. Thorsby7Kjetil Retterstøl8Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway; Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway; For correspondence: Alexander Bauer WestbyeLipid Clinic, Oslo University Hospital, Aker, Oslo, NorwayHormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway; Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, NorwayLipid Clinic, Oslo University Hospital, Aker, Oslo, NorwayNorwegian National Unit for Diagnostics of Congenital Metabolic Disorders, Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Metabolic Molecular Biology Research Group, Oslo University Hospital, Rikshospitalet, Oslo, NorwayDivision of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Chemistry, Karolinska University Hospital, Stockholm, SwedenHormone Laboratory, Department of 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, NorwayLipid Clinic, Oslo University Hospital, Aker, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDisease-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. 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-Opitz syndrome (SLOS; n = 1), and cerebrotendinous xanthomatosis (CTX; n = 1) were analyzed. 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. 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.http://www.sciencedirect.com/science/article/pii/S0022227524002037sitosterolcampesterolstigmasterol7-dehydrocholesterolcholestanolLC-MS/MS |
| spellingShingle | Alexander Bauer Westbye Lili L. Dizdarevic Sandra R. Dahl Emil Andreas Asprusten Yngve Thomas Bliksrud Anita Lövgren Sandblom Ulf Diczfalusy Per M. Thorsby Kjetil Retterstøl A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome Journal of Lipid Research sitosterol campesterol stigmasterol 7-dehydrocholesterol cholestanol LC-MS/MS |
| title | A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome |
| title_full | A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome |
| title_fullStr | A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome |
| title_full_unstemmed | A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome |
| title_short | A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome |
| title_sort | sterol panel for rare lipid disorders sitosterolemia cerebrotendinous xanthomatosis and smith lemli opitz syndrome |
| topic | sitosterol campesterol stigmasterol 7-dehydrocholesterol cholestanol LC-MS/MS |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524002037 |
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