To explore the genetic variant spectrum and epidemiological characteristics of Familial hypercholesterolemia (FH) patients in a regional population. A retrospective analysis was carried out on exome data from 15 841 unrelated patients undergoing trio-whole exome sequencing and couples undergoing comprehensive carrier screening at the Affiliated Women and Children's Hospital of Ningbo University from January 2022 to June 2025. The analysis focused on FH-associated LDLR, APOB, and PCSK9 genes recommended by the American College of Medical Genetics and Genomics (ACMG) as secondary findings with clinical actionability. Pathogenic and likely pathogenic variants with clear pathogenic effects were reported based on the latest ACMG variant interpretation standards. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: NBFE-2025-KY-178). Through the analysis of 15 841 exome sequencing datasets, 145 FH-associated gene variant carriers were identified, with a carrier rate of 0.92%, and 46 distinct variant sites were detected. Among these, LDLR gene variants accounted for 75.17%, comprising 37 variant sites, with c.268G>A (p.Asp90Asn), c.1747C>T (p.His583Tyr) and c.1879G>A (p.Ala627Thr) being high-frequency variants. APOB gene variants accounted for 22.76%, comprising 6 variant sites, with c.10579C>T (p.Arg3527Trp) being a high-frequency variant. PCSK9 gene variants accounted for 2.07%, comprising 3 variant sites. Three previously unreported variants were identified, including one in the LDLR gene, namely c.394_397delinsGA (p.R132Efs*47), and two in the APOB gene, namely c.10696del (p.Ser3566ValfsTer8) and c.2517del (p.Thr840Leufs*23). The two APOB variant carriers exhibited low levels of low-density lipoprotein cholesterol, consistent with the diagnosis of familial hypobetalipoproteinemia (FHBL). Above findings revealed the characteristics of FH-associated gene variant spectrum in a large regional population, which provided evidence-based support for proactive prevention and precision treatment.

Apolipoprotein B–containing (APOB-containing) lipoproteins contribute to atherosclerosis by entering the arterial wall through the endothelial cell (EC) surface receptors scavenger receptor-BI (SR-BI) and activin receptor-like kinase 1 (ALK1). We used N-terminal fragments of APOB, molecular modeling, and site-directed mutagenesis to identify and block the binding of chylomicrons and LDL to these receptors in cells and mice. We discovered that different APOB regions interact with SR-BI and ALK1 expressed on ECs. APOB48 lipoproteins were only internalized by SR-BI. A fragment of APOB comprising 18% of the N-terminal sequence, APOB18, reduced the uptake and transport of both chylomicrons and LDL by ECs, whereas a shorter fragment, APOB12, only blocked ALK1-mediated uptake of APOB100-containing lipoproteins. Importantly, overexpressing APOB18 decreased atherosclerosis in hypercholesterolemic mice. These findings identify the N-terminal region of APOB as the cause of atherosclerosis and illustrate an approach to treating or preventing vascular disease.

Patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) undergoing lower extremity revascularization (LER) face high risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), despite guideline-directed lipid-lowering therapy. Apolipoprotein B100 (ApoB100), reflecting total atherogenic particle number, may identify residual risk beyond LDL-cholesterol (LDL-C). Therefore, we investigated whether baseline ApoB100 levels independently predict MACE and MALE beyond conventional risk factors in this high-risk population. In this prospective cohort study, 167 T2DM patients with CLTI undergoing LER were followed for 12months with visits at 1, 3, 6, and 12months post-procedure. We measured baseline ApoB100 and assessed its ability to predict MACE, MALE, and composite endpoints, adjusting for clinical covariates. Composite events occurred in 49.1% of patients, MACE in 24%, and MALE in 35.3%. ApoB100 levels were significantly higher in event groups (composite: 62.1 vs 38.0mg/dL, p < 0.01; MACE: 66.1 vs 44.4mg/dL, p < 0.01; MALE: 61.0 vs 42.4mg/dL, p < 0.01). Multivariable analyses confirmed ApoB100 as an independent predictor (composite OR 1.14 per mg/dL, 95% CI 1.08-1.20, p < 0.01; MACE OR 1.10, p < 0.01; MALE OR 1.05, p < 0.01). ROC analysis demonstrated excellent predictive accuracy for ApoB100 (AUC 0.86, 95% CI 0.80-0.91), with optimal ROC-derived cut-off of 56.6mg/dL. Adding baseline ApoB100 to conventional risk factors significantly improved model discrimination (AUC gains 0.08-0.15, all p < 0.01), while Kaplan-Meier curves by cut-off effectively stratified early events (log-rank p < 0.001). Elevated baseline ApoB100 independently predicted MACE, MALE, and composite events post-LER in T2DM-CLTI patients, substantially improving clinical risk models. Integrating ApoB100 into post-LER management algorithms could refine individualized therapeutic strategies, especially in patients with residual atherogenic risk despite optimal LDL-C control.

Smoking has a significant effect on plasma lipid concentrations, especially high‑density lipoprotein (HDL)-associated cholesterol and its distribution across HDL subfractions, which are critical for cardiovascular health. The present study aimed to investigate the association between smoking and HDL‑cholesterol (HDL‑C) concentration, as well as the cholesterol distribution between different HDL subfractions, and other lipid parameters, including total cholesterol (TC), low‑density lipoprotein cholesterol (LDL‑C), triglycerides (TG), apolipoprotein AI (ApoAI), apolipoprotein B100 (ApoB100), and the TG/HDL‑C and ApoB100/ApoAI ratios, in a Hungarian cohort of 314 (137 nonsmokers and 177 smokers). HDL‑associated cholesterol was fractionated into ten electrophoretic subfractions (HDL‑1 to HDL‑10) and three subclasses (HDL‑L, HDL‑I, HDL‑S) using the Lipoprint® HDL system. Smoking exposure was characterized using five indicators: current smoking status, cigarettes per day (CPD), duration of smoking (DoS), pack‑years, and the Heaviness of Smoking Index (HSI). Multiple regression models were applied, and significance was defined as p < 0.05 after Benjamini-Hochberg correction. All smoking‑related indicators were associated with a decrease in the cholesterol content of HDL subfractions. The strongest associations were observed for HDL‑4, HDL‑5, HDL‑6, and HDL‑7 (p < 0.001-0.033), as well as for the HDL‑I subclass (p < 0.001). Regarding the broader lipid profile, all indicators were significantly associated with lower HDL‑C (p < 0.001) and ApoAI (p = 0.001-0.003), and higher TG (p = 0.012-0.036), TG/HDL‑C ratio (p < 0.001-0.004), and ApoB100/ApoAI ratio (p < 0.001-0.015). In conclusion, smoking significantly reduces the cholesterol content of HDL subfractions, particularly within HDL‑4 to HDL‑7 and the HDL‑I subclass. Although total cholesterol levels were not significantly altered, smoking induced an atherogenic shift in lipid composition by lowering HDL‑C and increasing TG levels, which may contribute to or accelerate the development of atherosclerosis.

Angiopoietin-like protein 3 (ANGPTL3) is a key circulating regulator of triglyceride metabolism and a promising pharmacological target. The physiological consequences of profound ANGPTL3 deficiency can be explored in individuals with inherited loss-of-function (LOF) variants, who show reduced lifetime risk of atherosclerotic cardiovascular disease. ApoB48, apoB100 and TG metabolism were investigated in chylomicrons, VLDL1, VLDL2, IDL and LDL in 3 ANGPTL3 LOF homozygotes (undetectable plasma ANGPTL3), 4 LOF heterozygotes (ANGPTL3 45.0±7.4ng/mL) and 10 matched controls (ANGPTL3 110.5±27.6ng/mL). Studies were performed under post-prandial conditions to comprehensively characterize TG transport and apoB-containing lipoprotein kinetics. Chylomicron and very-low-density lipoproteins (VLDL) production rates were similar in ANGPTL3-deficient subjects and controls. The defining abnormality in LOF homozygotes was the extremely rapid lipolysis of chylomicrons and VLDL, with circulating residence times of minutes rather than hours and accelerated conversion of VLDL to IDL and LDL. LDL particles in LOF homozygotes were TG-enriched, cholesterol-depleted, metabolically heterogeneous and cleared more rapidly than in controls or LOF heterozygotes. LOF heterozygotes showed a less pronounced increase in chylomicron and VLDL lipolysis, with normal IDL and LDL kinetics. Complete loss of ANGPTL3 results in a rapid acceleration of the triglyceride-rich lipoprotein lipolysis pathway and promotes the formation of metabolically and compositionally abnormal LDL with accelerated clearance. These findings provide mechanistic insight into ANGPTL3 deficiency and are directly relevant for the development and safety assessment of ANGPTL3-targeted therapies.

Several studies have investigated the clinical and immunological aspects of medication-related osteonecrosis of the jaw (MRONJ). However, the underlying immunological mechanisms and signaling pathways involved in its pathophysiology remain incompletely understood. This systematic review and meta-analysis, complemented by bioinformatics analyses, aimed to identify proteomic biomarkers associated with MRONJ. Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library, and VHL) were searched, along with gray literature and manual searches. Observational studies in English comparing proteomic profiles of individuals with and without MRONJ were included. Study selection and data management were conducted using EndNote™ X8 and Rayyan.ai, and risk of bias was assessed using the QUADOMICS tool. Functional enrichment analysis was performed using g:Profiler and Reactome, and interaction networks were constructed using GeneMANIA, STRING, and MetaboAnalyst (Cytoscape program; version 3.10.1). Meta-analysis was performed in RStudio (R-4.5, Rstudio extension 2025.05.1+513) (α = 0.05). Three studies were included in the review, and two in the meta-analysis. The meta-analysis showed higher salivary levels of Apolipoprotein B-100 (APOB), Apolipoprotein A-II (APOA2), and Heparin Cofactor 2 (SERPIND1) in MRONJ patients, while the protein Keratin (KRT16) showed reduced levels without statistical significance. Bioinformatics analyses indicated involvement in lipid metabolism, impaired tissue repair, and inflammatory and immune responses. These findings suggest altered salivary proteomic signatures in MRONJ for APOB, APOA2, SERPIND1, and KRT16 proteins.

APOB-100 (apolipoprotein B100) is the obligate structural protein of very low-density lipoprotein (VLDL), intermediate density lipoprotein, and low-density lipoprotein (LDL), with each atherogenic particle containing a single copy. Because circulating APOB concentration reflects particle number, it has emerged as a clinically important marker that may outperform LDL cholesterol in cardiovascular risk prediction. Historically, the large size, lipid dependence, and conformational diversity of APOB have hindered a detailed structural understanding. However, recent advances in cryo-electron microscopy and integrative modeling have transformed this landscape, yielding near-atomic models of APOB organization on human LDL and defining the structural basis for receptor recognition. This review traces the evolution of APOB structural concepts from its discovery as the main LDL scaffold to contemporary cryo-electron microscopy-derived architectures. The new structures reveal an extended scaffold that encircles the particle, accommodates large changes in lipid cargo, and presents multiple interaction surfaces for the LDL receptor. The new models reconcile decades of mutagenesis, antibody mapping, and cross-linking data and provide a mechanistic framework for understanding familial hypercholesterolemia variants, receptor binding stoichiometry, and the structural transitions that occur during VLDL to LDL remodeling. Despite these advances, intrinsic heterogeneity in particle size, lipid composition, and protein conformation imposes fundamental limits on achievable resolution, and we argue that APOB should be viewed as a dynamic structural ensemble rather than a single static molecule. Future work will require integration of structural models with targeted biochemical studies to define cooperative receptor binding mechanisms, structural determinants of remnant clearance, and the basis for association with exchangeable apolipoproteins and lipolysis regulators. Extending cryo electron microscopy to LDL subpopulations like lipoprotein(a) and VLDL remnants promises to establish new frameworks for linking APOB architecture to lipoprotein metabolism and cardiovascular disease.

Obesity is an important risk factor for cardiometabolic disease, including dyslipidemia and atherosclerotic cardiovascular disease. Although the role of the liver in dyslipidemia is established, the contribution of adipose tissue is less clear. This study aims to clarify the role of adipose tissue in lipid metabolism and dyslipidemia. We conducted a cross-sectional analysis of 125 patients from the BARIA (The Immune System and Microbial Tone in Relation to NAFLD/NASH Before and After Bariatric Surgery in the Morbidly Obese in Amsterdam) longitudinal cohort study undergoing bariatric surgery. Comprehensive phenotyping included fasting untargeted plasma metabolomics, lipid, lipoprotein, adipokine profiling, RNA sequencing, and fecal shotgun metagenomics. Tissue transcriptomic and plasma metabolites were compared between individuals with and without dyslipidemia. Dyslipidemia was present in 43 of 125 individuals (34.4%), with higher triglycerides (1.62 versus 1.24 mmol/L), apoB (apolipoprotein B; 93.15 versus 81.81 mg/dL), and lower high-density lipoprotein (1.02 versus 1.35 mmol/L) and apoAI (136.40 versus 161.35 mg/dL). Plasma adipokines showed limited differences: leptin concentrations were lower in dyslipidemia in unadjusted analysis but reduced after adjustment for age, sex, and body weight (adjusted P=0.057). RNA sequencing identified altered gene expression of liver, jejunum, visceral and subcutaneous adipose tissue, most pronounced in subcutaneous adipose tissue. Dyslipidemia was associated with adipose tissue pathways related to inflammation, oxidative stress, and adipogenesis. Plasma metabolomics revealed associations with endocannabinoid-like, secondary bile acid, plasmalogen, butyrate, and sphingolipid metabolites. Gut metagenome analysis found modest differences. Dyslipidemia in obesity is associated with transcriptomic alterations in adipose tissue, including subcutaneous adipose tissue, involving inflammation, oxidative stress, and adipogenesis. These findings support a role of adipose tissue in lipid regulation beyond hepatic pathways.

Jejunal histopathology, metagenome, and mucosal transcriptome of broilers after an enteric challenge and fed diets with different fiber types and concentrations.

The diagnosis of premature coronary heart disease (PCHD) continues to pose challenges. miR-302a-3p serves as a potential diagnostic marker. This study investigated the diagnostic value of the combination serum miR-302a-3p and LDL-C for PCHD. This study encompassed a total of 116 patients with coronary artery stenosis (CAS), 116 patients with PCHD, and 108 control subjects. The levels of miR-302a-3p, TNF, IL6, and IL1B were detected by RT-qPCR. ROC curves and logistic regression analysis were used to evaluate diagnostic value and risk factors for disease progression, respectively. Invitro models of HUVECs were established by treating the cells with ox-LDL. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. SOD and MDA were assessed using commercial kits. Serum levels of miR-302a-3p and LDL-C were increased in both the CAS and PCHD groups. miR-302a-3p, LDL-C, Apo B-100, and Gensini scores are independent risk factors for the progression of CAS to PCHD. The AUC of the combined diagnostic model of miR-302a-3p and LDL-C for differentiating PCHD from the control group was 0.902, whereas the diagnostic value of miR-302a-3p alone was 0.885. In cellular experiments, inhibition of miR-302a-3p can mitigate the release of inflammatory factors and oxidative stress induced by ox-LDL. miR-302a-3p serves as an independent risk factor for PCHD. The combination of miR-302a-3p with LDL-C can significantly enhance the accuracy of diagnostic value. miR-302a-3p may participate in the pathological process of PCHD, and its function is related to inflammatory responses and oxidative stress.

Acute myeloid leukemia (AML) faces significant challenges in the development of novel therapeutic strategies due to drug resistance and disease relapse. Therefore, this study aims to identify new therapeutic targets for AML using a drug-target Mendelian randomization approach. Summary-level data on low-density lipoprotein (LDL)-related traits were obtained from the GWAS data available on the IEU Open GWAS platform, and AML-associated genetic data were sourced from the GWAS Catalog. Seven genes involved in LDL metabolism were selected as potential drug targets: Apolipoprotein A4 (APOA4), Apolipoprotein B (APOB), Apolipoprotein C1 (APOC1), Apolipoprotein E (APOE), Cholesteryl Ester Transfer Protein (CETP), LDL Receptor (LDLR), and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). The inverse-variance weighted (IVW) method was used as the primary analytical approach, with supplementary analyses conducted using MR-Egger regression, weighted median, simple mode, and weighted mode methods to validate the findings. 1. Drug-target Mendelian randomization analysis revealed that lowering LDL levels by targeting and inhibiting APOB may increase the risk of AML, with rs13392272 identified as a potential functional locus in this process. 2. Further validation showed that targeting and inhibiting APOB to reduce its own levels may also increase the risk of AML, with rs693 considered a potential functional locus involved in this effect.

Hypercholesterolemia is a common metabolic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, a major risk factor for cardiovascular disease. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and lipid metabolism. In this study, in silico analysis revealed that miR-30b-3p could potentially target Apolipoprotein B (APOB), Proprotein convertase subtilisin/kexin type 9 (PCSK9), and Cholesteryl ester transfer protein (CETP). miR-30b-3p binding sites in the 3'-untranslated regions (UTRs) of PCSK9, APOB, and CETP were predicted and validated by dual luciferase reporter assays. Luciferase assays indicated significant reducing reporter activity (PCSK9: 49%, APOB: 39%, CETP: 86%). miR-30b-3p overexpression decreased mRNA levels of PCSK9, APOB, and CETP, with reduced PCSK9/ApoB protein but unchanged CETP protein. miR-30b-3p could play a regulatory role in lipid metabolism by targeting PCSK9 and APOB, reducing LDL levels in hepatocytes. Huh-7 cells underwent miR-30b-3p overexpression via lentiviral transduction and the expression of genes/proteins were assessed by quantitative PCR and western blot. LDL and high-density lipoprotein (HDL)-associated proteins in the culture media supernatant were measured to evaluate functional lipid changes. LDL-associated protein decreased in the conditioned medium, whereas HDL-associated readouts remained unchanged, leading to a lower LDL/HDL ratio, indicating impact on lipid homeostasis. This study aimed to investigate the effects of miR-30b-3p on the expression and function of the mentioned genes and the outcome of this intervention on lipid metabolism. These findings propose miR-30b-3p as a promising therapeutic candidate for hypercholesterolemia, warranting further in vivo validation.

Familial hypercholesterolemia (FH), primarily caused by pathogenic LDLR, APOB, or PCSK9 variants, results in elevated LDL-C and increased cardiovascular risk. Genetic testing offers the definitive diagnosis, yet global approaches to FH genetic testing remain unstandardized. We investigate current testing practices worldwide and provide relevant recommendations. A survey was distributed to national lead-investigators (NLIs) of 68 countries in the FH-Studies Collaboration, assessing referral criteria, assay methodologies, target genes, and pathogenicity interpretation methods. NLIs from centres in 55/68 countries (81%) responded, spanning Africa (N=2), Americas (N=6), Asia (N=20), Europe (N=26), and Oceania (N=1). DLCN scores were the most common reason for referral to genetic testing (adults:72%; children:57%). Simon Broome and MEDPED criteria were reported only by centres from high-income countries (adults: 7% and 2%; children: 12% and 2%). Methods for testing in index versus non-index cases were significantly different (p <0.001). Next-generation sequencing (NGS) was the predominant assay method for index cases (62%), while Sanger sequencing was favoured for non-index (71%). However, these testing techniques did not differ between centres from high- and non-high-income countries for index cases (p=0.74) and non-index cases (p=0.49). Copy-number variants (CNVs) were assessed by 65% of centres, with most integrating CNV analysis into NGS platforms (86%) and others (14%) using multiplex ligation-dependent probe-amplification (MLPA) or microarrays. Screening encompassed LDLR (100%), APOB (97%), PCSK9 (95%), and other genes. Most centres (96%) incorporated pathogenicity interpretation into their reports, adhering largely to American College of Medical Genetics and Genomics guidelines. FH genetic testing practices vary widely across countries surveyed, emphasizing the need for global standardization to enhance accuracy and comparability of FH diagnoses worldwide. We suggest that genetic testing should include the three FH-causing genes and ideally the five associated/phenocopy genes.

Parallel screening strategies reveal distinct phenotypic and genotypic profiles of familial hypercholesterolemia in children and adults

Genetic dyslipidemias.

Lipoprotein(a) [Lp(a)] is a causal and independent cardiovascular risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis, with elevated levels observed in approximately 20% of the general population. Plasma Lp(a) concentrations are predominantly determined by genetic factors, particularly polymorphisms of the LPA gene, which modulate apolipoprotein(a) [apo(a)] size and influence its hepatic synthesis. Structurally, Lp(a) consists of an LDL-like particle containing apolipoprotein B100, covalently bound to apo(a), conferring markedly enhanced atherogenic, pro-inflammatory, and prothrombotic properties compared with an LDL particle. In the absence of therapies specifically approved for Lp(a) reduction, current clinical management relies on an intensive approach to global cardiovascular risk reduction. ESC/EAS guidelines recommend aggressive lowering of LDL cholesterol, particularly through high-intensity statin therapy and, in patients at high or very high risk, the addition of ezetimibe and PCSK9 inhibitors, in order to mitigate the residual risk associated with elevated Lp(a) levels. Lipoprotein apheresis represents the only intervention capable of producing a substantial and immediate reduction in Lp(a); however, its use is limited to selected patients due to its invasive nature and limited availability. In parallel, innovative therapies targeting LPA gene silencing-such as antisense oligonucleotides and small interfering RNA-as well as oral agents inhibiting Lp(a) assembly, are in advanced stages of development. These approaches have demonstrated Lp(a) reductions of up to 80-90%, offering concrete prospects for a causal therapeutic strategy, pending the results of cardiovascular outcome trials.

Tandem repeats matter for the functional versatility of giant proteins.

Triazine Thiols Decrease Apolipoprotein B Secretion From Hepatocytes Through Inhibition of Human Carboxylesterase 1

High target selectivityis a crucial factor in aptamerperformanceand practical applicability. The selectivity of four DNA aptamers(AP07, AP11, AP25, and AP29) toward oxidized low-density lipoprotein(oxLDL) was examined through computational prediction and experimentalvalidation. Molecular dynamics simulations, combined with molecularmechanics generalized Born surface area (MM/GBSA) analysis, were employedto evaluate binding preferences against apolipoprotein (apo) B100(apoB100) of native low-density lipoprotein (LDL), oxidized apoB100of oxLDL, apoA1 of high-density lipoprotein (HDL), apoC1/apoE of very-low-densitylipoprotein (VLDL), and albumin. Among the candidates, AP11 revealedthe strongest predicted affinity and selectivity toward oxidized apoB100,exhibiting the lowest binding free energies of −344.52 ±18.37 kcal/mol. Experimental validation using an aptamer-based electrochemicalassay confirmed the computational predictions, with AP11 displayinghigh selectivity for the entire oxLDL and cross-reactivity below 6%toward LDL, HDL, VLDL, and albumin. Structural analysis indicatedthat AP11 preserves key conformational motifs upon complex formation,contributing to the oxLDL–aptamer interaction. This integratedcomputational–experimental framework provides a robust strategyfor evaluating and optimizing aptamer selectivity toward complex biomoleculartargets.

Fatty liver is a leading cause of chronic liver disease in children, most often due to metabolic dysfunction-associated steatotic liver disease (MASLD). Fatty liver in lean or younger children may indicate underlying metabolic or genetic disorders, such as familial hypobetalipoproteinemia (FHBL). We examined the importance of considering familial hypobetalipoproteinemia (FHBL) in children presenting with fatty liver. This case series includes seven patients with FHBL from three families, treated at two medical centers. Clinical, laboratory, imaging, and genetic data were collected from the medical records. Four patients were male. The mean age at diagnosis was 15.3 years (range: 4-38). All the index patients were children or adolescents presenting with fatty liver. Genetic evaluation revealed biallelic variants in the microsomal triglyceride transfer protein (MTTP) gene in two siblings and heterozygous variants in the apolipoprotein B (APOB) gene in five patients. The mean body mass index was 27 kg/m2, and two patients had a BMI above 30 kg/m2. The median follow-up (FU) time was 12 months (interquartile range [IQR]: 1-57 months). Liver enzymes were elevated in three patients (range: 50-300 IU/L); median aspartate aminotransferase and alanine aminotransferase levels were 30 IU/L (IQR: 26-40.75) and 32 IU/L (IQR: 24.5-74), respectively. The median triglyceride, low-density lipoprotein, and apolipoprotein B levels were 74 mg/dL (IQR: 62-125), 55.3 mg/dL (IQR: 30-84.5), and 39.5 mg/dL (IQR: 35.2-43), respectively. FHBL should be considered a potential diagnosis in children with fatty liver and may coexist with other contributing etiologies such as obesity.