Key result
Metabolomic profiling using a combined model of seven metabolites correctly diagnosed 91.3% of homozygous familial hypercholesterolemia cases with an area under the curve of 0.939.
Why the study?
Genetic testing for HoFH is expensive in China and LDL-C levels overlap considerably between HoFH and HeFH, creating a need for cost-effective screening.
Does metabolomic profiling accurately differentiate homozygous from heterozygous familial hypercholesterolemia in Chinese patients with severe hypercholesterolemia?
Case-Control (n=170)
Does metabolomic profiling accurately differentiate homozygous from heterozygous familial hypercholesterolemia in Chinese patients with severe hypercholesterolemia?
Effect estimate: AUC 0.939
Metabolomic profiling provides a highly accurate and cost-effective method to preselect patients with severe familial hypercholesterolemia for genetic confirmation of the homozygous phenotype.
Metabolomic profiling may aid HoFH differentiation from severe HeFH where genetic testing is costly; leaves open clinical adoption pending prospective validation.
Homozygous familial hypercholesterolemia (HoFH) is a rare inborn-errors-of-metabolism disorder characterized by devastatingly elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. The gold standard for screening and diagnosing HoFH is genetic testing. In China, it is expensive and is always recommended for the most likely HoFH subjects with aggressive LDL-C phenotype. However, the LDL-C levels of HoFH patients and a substantial proportion of heterozygous FH (HeFH) patients overlapped considerably. Here, we performed a cost-effective metabolomic profiling on genetically diagnosed HoFH (n = 69) and HeFH patients (n = 101) with overlapping LDL-C levels, aiming to discovery a unique metabolic pattern for screening homozygotes in patients with severe FH. We demonstrated a differential serum metabolome profile in HoFH patients compared to HeFH patients. Twenty-one metabolomic alterations showed independent capability in differentiating HoFH from severe HeFH. The combined model based on seven identified metabolites yielded a corrected diagnosis in 91.3% of HoFH cases with an area under the curve value of 0.939. Collectively, this study demonstrated that metabolomic profiling serves as a useful and economical approach to preselecting homozygotes in FH patients with severe hypercholesterolemia and may help clinicians to conduct selective genetic confirmation testing and familial cascade screening.
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Du et al. (2023) conducted a case-control in Severe Familial Hypercholesterolemia (n=170). Metabolomic profiling vs. Heterozygous familial hypercholesterolemia (HeFH) patients was evaluated on Corrected diagnosis of HoFH (AUC 0.939). Metabolomic profiling using a combined model of seven metabolites correctly diagnosed 91.3% of homozygous familial hypercholesterolemia cases with an area under the curve of 0.939.
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