Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literature

Abstract Background Mutations in the ABCG5 gene can cause sitosterolemia, which is a rare lipid metabolism disorder characterized by impaired regulation of phytosterols, leading to their excessive accumulation in tissues and organs, which triggers various complications. If left untreated, it may cau...

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Main Authors: Xiaobing Sun, Jiong Wu, Pu Chen, Ruiqing He, Ting Li, Qingwen Zeng, Qi Hou
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Medical Case Reports
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Online Access:https://doi.org/10.1186/s13256-025-05439-0
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author Xiaobing Sun
Jiong Wu
Pu Chen
Ruiqing He
Ting Li
Qingwen Zeng
Qi Hou
author_facet Xiaobing Sun
Jiong Wu
Pu Chen
Ruiqing He
Ting Li
Qingwen Zeng
Qi Hou
author_sort Xiaobing Sun
collection DOAJ
description Abstract Background Mutations in the ABCG5 gene can cause sitosterolemia, which is a rare lipid metabolism disorder characterized by impaired regulation of phytosterols, leading to their excessive accumulation in tissues and organs, which triggers various complications. If left untreated, it may cause serious issues, often presenting first as xanthomas on the skin and other tissues. Case presentation A 9-year-old female Chinese Zhuang patient developed her first xanthomas on her knees at the age of 4, which progressively spread across her body over the years. Initial blood tests revealed elevated plasma cholesterol and low-density lipoprotein, and she was misdiagnosed with familial hypercholesterolemia, leading to ineffective treatment. Despite visiting several hospitals, the underlying cause remained unidentified, and the patient was eventually admitted to our hospital for further evaluation. The complete blood count showed mild hypochromic microcytic anemia and blood smears showed microcytic hypochromic anemia and the presence of giant platelets in the peripheral blood. Plasma phytosterol profiling revealed significantly elevated phytosterol levels, and whole exome sequencing detected a homozygous mutation in the ABCG5 gene (c.751C > T, p.Q251*). On the basis of these findings, the patient was diagnosed with sitosterolemia. Her parents and younger brother were found to carry the heterozygous mutation but exhibited no clinical symptoms. In addition, iron metabolism tests and DNA copy number multidetection technology, along with single nucleotide polymorphism typing, revealed that the patient also had a silent alpha-thalassemia trait (genotype: HBA, -α3.7/αα). Conclusion Sitosterolemia is a rare lipid metabolism disorder that should be considered in patients presenting with multiple xanthomas, severe hypercholesterolemia, or elevated low-density lipoprotein-cholesterol levels. Diagnosis can be confirmed through phytosterol detection and molecular testing. Early diagnosis allows for dietary recommendations-such as restricting cholesterol and phytosterol intake-and, if necessary, treatment with medications such as ezetimibe. As we know, alpha-thalassemia is able to cause microcytosis and phytosterolemia may cause stomatocytosis in peripheral blood. However, there are no reports of two gene mutations occurring simultaneously in the same individual, and no stomatocytosis was observed in our patient. Hence, this suggests that the mutual regulation of two diseases and the effects on red blood cell membranes may exist, and the underlying mechanisms of this phenomenon are valuable for further research.
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spelling doaj-art-61fbffa3dbc94bcb9abfa8c84094dcee2025-08-20T04:02:57ZengBMCJournal of Medical Case Reports1752-19472025-08-011911710.1186/s13256-025-05439-0Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literatureXiaobing Sun0Jiong Wu1Pu Chen2Ruiqing He3Ting Li4Qingwen Zeng5Qi Hou6Department of Laboratory, Shanghai Jiahui International HospitalDepartment of Laboratory, Shanghai Jiahui International HospitalDepartment of Laboratory Medicine, Zhongshan Hospital Fudan UniversityDepartment of Laboratory, Shanghai Jiahui International HospitalDepartment of Dermatology, Nanxiang Branch of Ruijin HospitalDepartment of Laboratory, Shanghai Jiahui International HospitalDepartment of Laboratory, Shanghai Jiahui International HospitalAbstract Background Mutations in the ABCG5 gene can cause sitosterolemia, which is a rare lipid metabolism disorder characterized by impaired regulation of phytosterols, leading to their excessive accumulation in tissues and organs, which triggers various complications. If left untreated, it may cause serious issues, often presenting first as xanthomas on the skin and other tissues. Case presentation A 9-year-old female Chinese Zhuang patient developed her first xanthomas on her knees at the age of 4, which progressively spread across her body over the years. Initial blood tests revealed elevated plasma cholesterol and low-density lipoprotein, and she was misdiagnosed with familial hypercholesterolemia, leading to ineffective treatment. Despite visiting several hospitals, the underlying cause remained unidentified, and the patient was eventually admitted to our hospital for further evaluation. The complete blood count showed mild hypochromic microcytic anemia and blood smears showed microcytic hypochromic anemia and the presence of giant platelets in the peripheral blood. Plasma phytosterol profiling revealed significantly elevated phytosterol levels, and whole exome sequencing detected a homozygous mutation in the ABCG5 gene (c.751C > T, p.Q251*). On the basis of these findings, the patient was diagnosed with sitosterolemia. Her parents and younger brother were found to carry the heterozygous mutation but exhibited no clinical symptoms. In addition, iron metabolism tests and DNA copy number multidetection technology, along with single nucleotide polymorphism typing, revealed that the patient also had a silent alpha-thalassemia trait (genotype: HBA, -α3.7/αα). Conclusion Sitosterolemia is a rare lipid metabolism disorder that should be considered in patients presenting with multiple xanthomas, severe hypercholesterolemia, or elevated low-density lipoprotein-cholesterol levels. Diagnosis can be confirmed through phytosterol detection and molecular testing. Early diagnosis allows for dietary recommendations-such as restricting cholesterol and phytosterol intake-and, if necessary, treatment with medications such as ezetimibe. As we know, alpha-thalassemia is able to cause microcytosis and phytosterolemia may cause stomatocytosis in peripheral blood. However, there are no reports of two gene mutations occurring simultaneously in the same individual, and no stomatocytosis was observed in our patient. Hence, this suggests that the mutual regulation of two diseases and the effects on red blood cell membranes may exist, and the underlying mechanisms of this phenomenon are valuable for further research.https://doi.org/10.1186/s13256-025-05439-0SitosterolemiaXanthomasPhytosterolFamilial hypercholesterolemia
spellingShingle Xiaobing Sun
Jiong Wu
Pu Chen
Ruiqing He
Ting Li
Qingwen Zeng
Qi Hou
Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literature
Journal of Medical Case Reports
Sitosterolemia
Xanthomas
Phytosterol
Familial hypercholesterolemia
title Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literature
title_full Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literature
title_fullStr Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literature
title_full_unstemmed Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literature
title_short Sitosterolemia carrying both ABCG5 and HBA gene mutations: a case report and review of the literature
title_sort sitosterolemia carrying both abcg5 and hba gene mutations a case report and review of the literature
topic Sitosterolemia
Xanthomas
Phytosterol
Familial hypercholesterolemia
url https://doi.org/10.1186/s13256-025-05439-0
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