Managing homozygous familial hypercholesterolaemia from cradle to grave.
OBJECTIVE
To describe the phenotypic and genotypic features and management of clinically homozygous familial hypercholesterolaemia (FH).


METHODS
An analysis of current knowledge based on personal experience and published evidence.


RESULTS
Atherosclerotic involvement of the aortic root is common in homozygous FH and can cause death before age 5. Receptor negative patients are at greatest risk, irrespective of whether they have identical mutations (homozygous) or dissimilar mutations (compound heterozygous).


CONCLUSIONS
Lipoprotein apheresis combined with high dose statin and ezetimibe slows but does not arrest progression of atherosclerosis. Adjunctive use of novel compounds such as lomitapide and evolocumab should facilitate achieving the latter objective by enhancing the reduction in LDL cholesterol.
Metabolic Medicine, Imperial College, Hammersmith Hospital, London, W12 0NN, UK. Electronic address: g.thompson@imperial.ac.uk.
Gilbert R
GR
Thompson
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000097:blood*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; C573412:LDLR protein, human; D011973:Receptors, LDL
Compound heterozygote; Homozygote; Hypercholesterolaemia; Lipoprotein apheresis