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IEMbase 0527: LDLR-related homozygous familial hypercholesterolemia

Scope

Field Value
IEMbase ID 527
Nosology 15.1.01.02
Gene LDLR
External IDs OMIM:143890; OMIM:606945; ORPHA:391665
Generated mapping UNMAPPED; best candidate Familial_Hypercholesterolemia.yaml
Candidate DisMech targets Familial_Hypercholesterolemia.yaml#Homozygous Familial Hypercholesterolemia
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents LDLR-related homozygous familial hypercholesterolemia, with hyperlipoproteinemia type 2A and HoFH as alternate labels. The record is marked autosomal recessive and treatable.

The biochemical signal is very high LDL cholesterol and Apo B with normal HDL cholesterol and triglycerides. Clinical rows include coronary atherosclerosis, myocardial ischemia, carotid stenosis, carotid and femoral bruits, aortic valve disease, calcified aortic valve, arcus cornealis, xanthelasma, and tendon xanthomas. Treatment rows include statins, ezetimibe, PCSK9 inhibitors, inclisiran, evinacumab, lomitapide, bile acid sequestrants, and low-fat diet.

DisMech phenotype coverage

The generated UNMAPPED status is a false negative. Familial_Hypercholesterolemia.yaml contains a homozygous FH subtype and LDLR mechanism coverage. The local file models reduced hepatic LDL receptor function, lifelong LDL cholesterol excess, childhood-to-adolescent severe atherosclerotic disease in HoFH, aortic valve disease, tendon and skin cholesterol deposition, and intensive LDL-lowering therapy.

Local coverage is also strong for HoFH-specific therapy, including evinacumab, lomitapide, PCSK9-directed therapies where residual LDLR function exists, LDL apheresis, statins, ezetimibe, diet, and last-resort liver transplantation context.

Concordance and completeness

Judgement: false negative; resolve to the local familial hypercholesterolemia file, specifically its homozygous FH / LDLR context.

IEMbase and DisMech agree on LDLR identity, severe LDL-C and Apo B elevation, cholesterol-deposition phenotypes, premature cardiovascular disease, aortic valve involvement, and combination LDL-lowering treatment. IEMbase adds compact bruit and specimen-level lipoprotein prompts.

Curation actions

  • Map this record to Familial_Hypercholesterolemia.yaml#Homozygous Familial Hypercholesterolemia.
  • Consider adding HoFH, hyperlipoproteinemia type 2A, and the IEMbase treatment list to alias/management checks if missing from future mapping data.
  • Preserve carotid/femoral bruits, Apo B, HDL, triglyceride, aortic-valve, and xanthoma rows as enrichment prompts.