IEMbase 0367: LDLR-related heterozygous familial hypercholesterolemia
Scope
| Field | Value |
|---|---|
| IEMbase ID | 367 |
| Nosology | 15.1.01.01 |
| Gene | LDLR |
| External IDs | OMIM:143890; OMIM:606945; ORPHA:391665 |
| Generated mapping | UNMAPPED; low candidate Familial_Hypercholesterolemia.yaml |
| Candidate DisMech targets | Familial_Hypercholesterolemia.yaml#Heterozygous FH/LDLR |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents LDLR-related heterozygous familial hypercholesterolemia, also listed as hyperlipoproteinemia type 2A. The record is autosomal dominant and reports prevalence text of approximately 1:500 heterozygotes and 1:1,000,000 homozygotes.
Characteristic rows include plasma Apo B, arcus cornealis, plasma LDL cholesterol, xanthelasma, and tendon xanthomas. Additional clinical rows include carotid bruits, femoral bruits, and myocardial ischemia. Biochemical rows include plasma Apo B, plasma HDL cholesterol, plasma LDL cholesterol, and serum triglyceride. Treatment rows include colesevelam, ezetimibe, low-fat diet, PCSK9 inhibitors, and statins.
DisMech phenotype coverage
The generated UNMAPPED status is a false negative. DisMech has a Familial Hypercholesterolemia file that explicitly covers heterozygous FH caused by one pathogenic allele in LDLR, APOB, or PCSK9. The local LDLR mechanism describes reduced hepatic LDL receptor function, impaired receptor-mediated LDL clearance, elevated LDL-C from birth, tendon xanthomas, premature ASCVD, and lifelong LDL-lowering therapy.
Local coverage is stronger for the hepatocyte LDL-clearance mechanism and the broader FH management model. IEMbase is stronger for bruits and specimen-level lipoprotein rows.
Concordance and completeness
Judgement: false negative; resolve to the local familial hypercholesterolemia LDLR/heterozygous FH context.
The resources agree on LDLR identity, autosomal dominant inheritance, heterozygous FH, elevated LDL cholesterol, tendon xanthomas, corneal arcus, premature atherosclerotic ischemic disease, statins, ezetimibe, PCSK9 inhibitors, and diet/lifestyle treatment context.
Curation actions
- Map this record to
Familial_Hypercholesterolemia.yaml, specifically the heterozygous FH and LDLR functional-defect context. - Consider future enrichment with carotid bruits, femoral bruits, Apo B, HDL cholesterol, triglyceride rows, colesevelam, and the IEMbase prevalence wording after source verification.
- Keep homozygous prevalence wording distinct from the heterozygous disease scope when importing any prevalence information.