Last update 01 Nov 2024

Sitosterolemia

Last update 01 Nov 2024

Basic Info

Synonyms

PHYTOSTEROLEMIA, Phytosterolaemia, Phytosterolemia

+ [21]

Introduction

An extremely rare autosomal recessive inherited disorder caused by mutations in the ABCG5 or ABCG8 genes. It is characterized by a defective sterolin transporter that impairs the elimination of plant sterols and, to a lesser degree, cholesterol from the body. These fatty substances build up in the tissues including arteries and skin, resulting in atherosclerosis and xanthomas.

Drugs associated with Sitosterolemia

Ezetimibe

Target

NPC1L1

Mechanism

NPC1L1 inhibitors [+1]

Active Org.

Merck Sharp & Dohme LLC [+3]

Originator Org.

Merck Sharp & Dohme Corp.

Active Indication

Homozygous familial hypercholesterolemia [+3]

Inactive Indication

Atherosclerosis [+7]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date25 Oct 2002

Clinical Trials associated with Sitosterolemia

CTR20243141 / Active, not recruitingNot Applicable

依折麦布片人体生物等效性试验

[Translation] Bioequivalence study of ezetimibe tablets in humans

主要目的：在健康男性与女性受试者中于空腹/餐后条件下，评价受试制剂依折麦布片（规格：10 mg，生产商：南京海鲸药业股份有限公司）和MSD Pharma（Singapore）Pte. Ltd.为持证商的参比制剂依折麦布片（益适纯®，规格：10 mg）的生物等效性。次要目的：观察受试制剂依折麦布片与参比制剂依折麦布片（益适纯®）在健康受试者中的安全性。

[Translation]

Primary objective: To evaluate the bioequivalence of the test preparation Ezetimibe Tablets (Specification: 10 mg, Manufacturer: Nanjing Haijing Pharmaceutical Co., Ltd.) and the reference preparation Ezetimibe Tablets (Ezetimibe®, Specification: 10 mg) of which MSD Pharma (Singapore) Pte. Ltd. is the licensee in healthy male and female subjects under fasting/postprandial conditions. Secondary objective: To observe the safety of the test preparation Ezetimibe Tablets and the reference preparation Ezetimibe Tablets (Ezetimibe®) in healthy subjects.

Start Date05 Aug 2024

Sponsor / Collaborator

Nanjing Haijing Pharmaceutical Co. Ltd.

CTR20241438 / CompletedNot Applicable

依折麦布片人体生物等效性研究

[Translation] Study on the bioequivalence of ezetimibe tablets in healthy volunteers

本试验旨在研究健康受试者单次空腹和餐后口服由华润赛科药业有限责任公司研制、生产的依折麦布片（10 mg）的药代动力学特征；以MSD International GmbH（Singapore Branch）生产的依折麦布片（益适纯®，10 mg）为参比制剂，比较两制剂中药动学参数Cmax、AUC0-t、AUC0-∞，评价两制剂的人体生物等效性，并观察两制剂在健康受试者中的安全性。

[Translation]

This study aimed to investigate the pharmacokinetic characteristics of ezetimibe tablets (10 mg) developed and produced by China Resources Saike Pharmaceuticals Co., Ltd. after single fasting and postprandial oral administration in healthy subjects; using ezetimibe tablets (Ezetimibe®, 10 mg) produced by MSD International GmbH (Singapore Branch) as the reference preparation, the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ of the two preparations were compared, the human bioequivalence of the two preparations was evaluated, and the safety of the two preparations in healthy subjects was observed.

Start Date08 May 2024

Sponsor / Collaborator

China Resources Saike Pharmaceutical Co., Ltd.

CTR20240830 / CompletedNot Applicable

依折麦布片（10mg）在中国健康受试者中空腹和餐后给药条件下随机、开放、单剂量、两序列、四周期、完全重复交叉生物等效性试验

[Translation] A randomized, open-label, single-dose, two-sequence, four-period, fully repeated crossover bioequivalence study of ezetimibe tablets (10 mg) in Chinese healthy subjects under fasting and fed conditions

主要研究目的：按有关生物等效性试验的规定，选择MSD PHARMA (Singapore) Pte. Ltd.为持证商的依折麦布片（商品名：Ezetrol（益适纯），规格：10mg）为参比制剂，对江苏复旦复华药业有限公司生产，翎耀生物科技（上海）有限公司提供的受试制剂依折麦布片（规格：10mg）进行空腹和餐后给药人体生物等效性试验，比较受试制剂中药物的吸收速度和吸收程度与参比制剂的差异是否在可接受的范围内，评价两种制剂在空腹和餐后给药条件下的生物等效性。次要研究目的：观察健康志愿受试者口服受试制剂依折麦布片（规格：10mg）和参比制剂依折麦布片（商品名：Ezetrol（益适纯），规格：10mg）的安全性。

[Translation]

Main purpose of study: According to the relevant provisions of bioequivalence test, Ezetrol Tablets (trade name: Ezetrol, specification: 10mg) of MSD PHARMA (Singapore) Pte. Ltd. as the licensee was selected as the reference preparation, and the test preparation Ezetrol Tablets (specification: 10mg) produced by Jiangsu Fudan Fuhua Pharmaceutical Co., Ltd. and provided by Lingyao Biotechnology (Shanghai) Co., Ltd. were subjected to human bioequivalence test on fasting and postprandial administration, to compare whether the absorption rate and degree of the drug in the test preparation were within the acceptable range with the reference preparation, and to evaluate the bioequivalence of the two preparations under fasting and postprandial administration conditions. Secondary purpose of study: To observe the safety of oral administration of the test preparation Ezetrol Tablets (specification: 10mg) and the reference preparation Ezetrol Tablets (trade name: Ezetrol, specification: 10mg) by healthy volunteers.

Start Date08 Apr 2024

Sponsor / Collaborator

Lingyao Biotechnology (Shanghai) Co., Ltd.

100 Clinical Results associated with Sitosterolemia

100 Translational Medicine associated with Sitosterolemia

0 Patents (Medical) associated with Sitosterolemia

479

Literatures (Medical) associated with Sitosterolemia

01 Sep 2024·Journal of Clinical Lipidology

Evaluation of plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects

Article

Author: Zhang, Yiqing ; Wu, Junfang ; Zhang, Yuxuan ; Wang, Luya ; Zhang, Jun ; Yu, Hao ; Chen, Yan ; Ren, Xuanru ; Zheng, Zhaohai ; Zeng, Hesong ; Li, Jialu

BACKGROUNDPatients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging.METHODSHere we retrospectively recruited seven families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned four groups.RESULTSAs expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these two groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis.CONCLUSIONOur study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.

01 Aug 2024·Clinica Chimica Acta

Dried blood spot-based free sterol signatures in sitosterolemia diagnostics

Article

Author: Choi, Man Ho ; Park, Mi Jung ; Moon, Ju-Yeon ; Lee, Ayoung ; Garg, Abhimanyu ; Son, Hyun-Hwa ; Yoo, Eun-Gyong ; Jung, Mo Kyung ; Kwon, Go Eun ; Rhie, Seonkyeong

BACKGROUNDSitosterolemia is a rare inherited lipid metabolic disorder characterized by increased levels of plant sterols and accelerated atherosclerosis. Although early detection is beneficial for the prevention of disease progression, it is largely underdiagnosed by routine screening based on conventional lipid profiles.MATERIALS AND METHODSA gas chromatography-mass spectrometry (GC-MS)-based profiling has been developed and validated to measure the levels of biologically active free sterols, including five endogenous sterols and three plant sterols (sitosterol, campesterol, and stigmasterol) in dried blood spot (DBS).RESULTSWithin- and between-run precisions were 1.4-11.1 % and 2.2-14.1 %, respectively, while the accuracies were all 86.3 ∼ 121.9 % with the correlation coefficients (r²) > 0.988 for all the sterols. In the patients (four girls and two boys, 6.5 ± 2.8 years), sitosterol levels were significantly increased, with an optimal cut-off value of 2.5 µg/mL distinguishing them from ninety-three age-matched healthy children. A cut-off value of 31.9 µg/mL differentiated the patients from six ABCG5/ABCG8 heterozygous carriers. In addition, the molecular ratios of sitosterol to cholesterol, desmosterol, and 7-dehydrocholesterol provided excellent cut-off values of 26.3, 67.6, and 21.6, respectively, to distinguish patients from both healthy controls and heterozygous carriers.CONCLUSIONSThe novel DBS-based GC-MS profiling of free sterols accurately identified patients with sitosterolemia, with a performance comparable to that of a serum assay. The DBS profiling could be more feasible method in clinical practice as well as population screening programs, and it can provide diagnostic cut-off values for individual plant sterols.

01 Jul 2024·Clínica e Investigación en Arteriosclerosis

Sitosterolemia familiar: reporte de dos casos en Colombia

Article

Author: Castillo, María Del Carmen ; Zapateiro, Jorge L ; Ruiz, María Elvira ; Nogueira, Juan Patricio ; Montoya, Laura ; Castellanos, Alejandro A

Sitosterolemia is an autosomal recessive and very rare disease. Its main characteristic is that there is a greater absorption and a decrease in the excretion of sterols, which leads to them being deposited in tissues. It is given by mutations in the ABCG5 or ABCG8 genes found on chromosome 2p21. In this clinical note, we describe the first two patients with familial sitosterolemia described in Colombia, brothers, one of them with xanthomas in extremities as the only symptom, and the other, completely asymptomatic. Genetic studies were performed as a diagnostic test in both patients, where a pathogenic homozygous variant could be identified in the ABCG8 gene in the first case (symptomatic), and a heterozygous variant in the ABCG8 gene in the second case (asymptomatic); the first patient has responded to treatment with ezetimibe. In conclusion, xanthomas should be studied in depth in pediatric age as they may be the only visible sign of such complex and hereditary diseases as familial sitosterolemia, which can be controlled and prevent cardiovascular complications of the disease.

News (Medical) associated with Sitosterolemia

17 Aug 2022

·www.prnewswire.com

Boston Heart Diagnostics Launches LipidSeq™-- An NGS Test for Common Genetic Disorders of Lipid Metabolism

FRAMINGHAM, Mass. , Aug. 17, 2022 /PRNewswire/ -- Boston Heart Diagnostics, part of the Eurofins network of companies, announces the launch of LipidSeq™, a revolutionary genetic test for cardiovascular disease. This saliva-based NGS test identifies the most common genetic causes of lipid and lipoprotein disorders. These disorders are associated with premature cardiovascular, pancreatic, kidney, and neurological diseases. Continue Reading When patients have very high levels of low-density lipoprotein cholesterol, triglycerides, or plasma sterols and/or very low levels of high-density lipoprotein cholesterol, there is a likelihood of a genetic mutation. Conditions detected by this 23-gene test include familial forms of hypercholesterolemia, lysosomal acid lipase deficiency, sitosterolemia, cerebrotendinous xanthomatosis, dysbetalipoproteinemia, hypertriglyceridemia, and HDL deficiency states including ApoA-I deficiency, Tangier disease, and LCAT deficiency, as well as other disorders. If there is a genetic basis for the patient's condition, understanding the specific mutation and associated disease can help guide treatment considerations, educate the patient about health risks, and encourage relatives to seek testing to determine if they, too, may be at risk. Boston Heart is the only commercial laboratory able to test biochemical and genetic contributors when diagnosing inherited disorders of lipid metabolism (Reference: Schaefer EJ, Geller AS, Endress G. The biochemical and genetic diagnosis of lipid disorders. Current Opinion in Lipidology 2019; 30:56-62.) Boston Heart Diagnostics announces the launch of LipidSeq™, a revolutionary genetic test for cardiovascular disease. Tweet this Testing of appropriate patients can be done at any age, which favors early identification and treatment of genetically influenced lipid and lipoprotein disorders. Early diagnosis and precision treatment can save lives, and have a significant clinical impact for practitioners, patients, and their families. LipidSeq was developed in collaboration with Eurofins laboratory partner Clinical Enterprise, which performs the genetic sequencing, and in consultation with Dr. Robert A. Hegele of Robarts Research Institute in London, Ontario. Healthcare providers may access this testing for their patients by signing up for an account with Boston Heart. The Boston Heart Customer Care department is available at 877.425.1252 or [email protected]. About Boston Heart Diagnostics Corporation Boston Heart Diagnostics, a subsidiary of Eurofins Scientific (EUFI.PA), is transforming the treatment of cardiovascular disease and related conditions by providing healthcare providers and their patients with novel, personalized diagnostics and integrated customized lifestyle programs that have the power to change the way clinicians and patients communicate about disease and improve health. For more information on Boston Heart Diagnostics, please visit SOURCE Boston Heart Diagnostics

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Sitosterolemia

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