| Domain | Core finding | Quantitative datum | Suggested ontology |
|---|---|---:|---|
| Disease identity | LDLR-related familial hypercholesterolemia is a highly penetrant co-dominant Mendelian disorder with lifelong elevation of LDL-C from birth and markedly increased premature ASCVD risk | HeFH usually LDL-C >190 mg/dL; HoFH often >400 mg/dL | MONDO:0007750; HP:0003124 |
| Genetics | Most molecularly confirmed FH is caused by pathogenic LDLR variants that reduce receptor-mediated LDL clearance; null and defective alleles produce severity spectrum | LDLR accounts for ~80–90% of genetically diagnosed FH; >2,300 unique LDLR variants reported | HGNC:6547; SO:0001583/0001587/0001574 |
| Biochemical phenotype | Core laboratory phenotype is elevated plasma LDL-C with elevated apoB; HoFH may also show elevated VLDL/IDL and reduced HDL in severe models | Pediatric PCSK9 meta-analysis: LDL-C −37.92%, apoB −33.67%, Lp(a) −16.94% | HP:0003124; HP:0012185; CHEBI:16129 |
| Physical signs | Classical stigmata include tendon xanthomas, corneal arcus, and periocular/cutaneous xanthomas in more severe disease | Tendon xanthomas seen in <15% and corneal arcus in ~30% of HeFH in a cited cohort context | HP:0000991; HP:0001085 |
| Cardiovascular complications | Untreated disease accelerates atherosclerosis, coronary disease, and in severe cases aortic valve/ascending aortic disease | Genetic FH with LDL-C >190 mg/dL conveys ~3.7-fold higher CHD risk than equally elevated LDL-C without an FH mutation | HP:0001677; HP:0001717; UBERON:0000948 |
| Diagnosis/screening | Diagnosis combines LDL-C level, family history, premature ASCVD, physical signs, and ideally confirmatory genetic testing; cascade screening is central | Opportunistic trigger LDL-C ≥190 mg/dL; screen at-risk children by age 5 years, or by 2 years if strong family history; suspected HoFH at newborn stage to 2 years | NCIT:C157171; HP:0031372 |
| Standard treatment | First-line care is intensive statin therapy plus ezetimibe, escalating to combination therapy to reach LDL-C targets | Statins lower LDL-C ~50–60% alone and ~65–70% with ezetimibe; bempedoic acid ~22.3% LDL-C reduction in clinical HeFH phenotype | NCIT:C29447; NCIT:C61731; NCIT:C88519 |
| LDLR-independent treatment | For severe disease, especially HoFH or null/null LDLR, receptor-independent therapies such as evinacumab and lomitapide are key; apheresis may still be required | Evinacumab lowers LDL-C by ~50% overall and ~43% even in null/null LDLR; ANGPTL3 mAb review cites ~50% LDL and ~47% TG reduction | NCIT:C158502; NCIT:C83818; NCIT:C15201 |
| Epidemiology | FH is common but substantially underdiagnosed worldwide | Prevalence ~1 in 311 globally; ~35 million people affected; only ~10% diagnosed worldwide | MONDO:0005439 |
| Models | Experimental systems recapitulate LDLR-FH across species for mechanism and therapy testing, from mouse to non-human primate | LDLR knockout mice show ~2-fold total cholesterol increase; six LDLR-KO cynomolgus monkeys generated with HoFH-like phenotype | NCBITaxon:10090; NCBITaxon:9541; CL:0000182 |


*Table: This table condenses the main disease-knowledge-base domains for LDLR-related familial hypercholesterolemia into ontology-ready findings and quantitative anchors. It is useful as a compact reference for curation and downstream structured annotation. (pqac-00000001, pqac-00000009, pqac-00000010, pqac-00000012, pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000020, pqac-00000021)*