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作者

Mengyuan Wu MSc Hongjiang Wu BSc Weihua Sun MSc Yan Sun MD Bingbing Wu MD Feihong Luo MD Zhou Pei MD Wei Lu MD

作者单位

⁵Shared corresponding authors ⁴National Children's Medical Center, Department of Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China (Feihong Luo, Zhou Pei, and Wei Lu) ³Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China (Yan Sun) ¹National Children's Medical Center, Center for molecular medicine, Children's Hospital of Fudan University, Shanghai, China (Mengyuan Wu, Hongjiang Wu, Weihua Sun, and Bingbing Wu) ²Shared first authors.

刊名

Journal of Clinical Lipidology

年份

2026

ISSN

1933-2874

关键词

Sitosterolemia Hypercholesterolemia Phytosterol Cholesterol ABCG5/8 Diagnostic biomarker

摘要

BACKGROUND Patients with sitosterolemia are often misdiagnosed as familial hypercholesterolemia because of overlapping lipid phenotypes. Sitosterol is considered a disease-specific biomarker; however, its diagnostic utility in highly heterogeneous populations—particularly among children—remains unclear. OBJECTIVE To evaluate the diagnostic value of phytosterol biomarkers and develop a multivariate model to improve the diagnostic accuracy of ST. METHODS We conducted a cross-sectional study of 3...更多

BACKGROUND Patients with sitosterolemia are often misdiagnosed as familial hypercholesterolemia because of overlapping lipid phenotypes. Sitosterol is considered a disease-specific biomarker; however, its diagnostic utility in highly heterogeneous populations—particularly among children—remains unclear. OBJECTIVE To evaluate the diagnostic value of phytosterol biomarkers and develop a multivariate model to improve the diagnostic accuracy of ST. METHODS We conducted a cross-sectional study of 379 children with suspected lipid disorders: ST , ABCG5/8 heterozygous carriers , genetically confirmed FH , individuals with FH-like , and healthy controls . Clinical characteristics, lipid profiles, phytosterols, liver enzymes, and genetic data were collected. The diagnostic performance of single biomarkers and a multivariate model was evaluated. A clinical gray zone based on sitosterol levels was defined to assess the models’ ability. RESULTS Sitosterol demonstrated near-perfect discrimination for ST in the overall population area under the curve , outperforming conventional lipid markers. However, substantial overlap in phytosterol distributions was observed among ST, heterozygotes, and FH-related phenotypes. Within the gray zone , the diagnostic performance of sitosterol declined markedly . The multivariable model demonstrated comparable overall performance but significantly improved discrimination in the gray zone , with good calibration and greater net clinical benefit. CONCLUSION Although sitosterol is highly effective for identifying ST, its diagnostic performance declines significantly in clinically significant gray zone cases. A combined sterol-based model improves diagnostic discrimination in these challenging scenarios and supports a stepwise diagnostic strategy for children with suspected ST.收起

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