Homozygous familial hypercholesterolemia
Synonyms: HoFH
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal dominant, Autosomal recessive
- Age of onset
- Neonatal
- Status
- active
A rare disorder of lipid metabolism characterized by severely elevated plasma total cholesterol, low-density lipoprotein (LDL) cholesterol levels, and subsequent premature formation of atherosclerotic plaques in the coronary arteries, proximal aorta, and other arteries, significantly increasing the risk of premature cardiovascular disease and death. Xanthomas of the skin and in tendons are also a hallmark of the disease. Lethality is high due to early complications, in particular myocardial infarction and aortic valvular disease.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Homozygous familial hypercholesterolemia | HoFH |
| fr | Hypercholestérolémie familiale homozygote | = en |
| de | Familiäre Hypercholesterinämie bei homozygoter Mutation | = en |
| es | Hipercolesterolemia familiar homocigota | = en |
| it | Ipercolesterolemia familiare omozigote | = en |
| nl | Homozygote familiale hypercholesterolemie | = en |
| pt | Hipercolesterolemia familiar homozigótica | = en |
| pl | Rodzinna hipercholesterolemia | = en |
| cs | Homozygotní familiární hypercholesterolémie | = en |
| uk | Гомозиготна сімейна гіперхолестеринемія | = en |
| zh | 纯合家族性高胆固醇血症 | = en |
| tr | Homozigot ailesel hiperkolesterolemi | = en |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 143890 | NTBT | validated | |
| OMIM | 144010 | BTNT | validated | |
| OMIM | 602247 | BTNT | validated | |
| OMIM | 603776 | BTNT | validated | |
| OMIM | 603813 | BTNT | validated | |
| ICD-10 | E78.0 | NTBT | attributed | validated |
| ICD-11 | 5C80.00 | NTBT | index | validated |
| MONDO | 0018328 | E | validated | |
| MeSH | D000090542 | E | validated | |
| UMLS | C0342881 | E | validated | |
| GARD | 10416 | E | validated | |
| MedDRA | 10057080 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (1):
- ORPHA:477811Rare hypercholesterolemia
rare inborn errors of metabolism; rare genetic diseases; rare endocrine diseases
No children.
Genes
6 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| ABCG5 | Candidate gene tested in | Not yet assessed | HGNC:13886 | ENSG00000138075 | 605459 | 2p21 | ATP binding cassette subfamily G member 5 | 20172523[PMID] |
| ABCG8 | Candidate gene tested in | Not yet assessed | HGNC:13887 | ENSG00000143921 | 605460 | 2p21 | ATP binding cassette subfamily G member 8 | 20172523[PMID] |
| APOB | Disease-causing germline mutation(s) in | Assessed | HGNC:603 | ENSG00000084674 | 107730 | 2p24.1 | apolipoprotein B | 24404629[PMID] |
| LDLR | Disease-causing germline mutation(s) in | Assessed | HGNC:6547 | ENSG00000130164 | 606945 | 19p13.2 | low density lipoprotein receptor | 24404629[PMID] |
| LDLRAP1 | Disease-causing germline mutation(s) in | Assessed | HGNC:18640 | ENSG00000157978 | 605747 | 1p36.11 | low density lipoprotein receptor adaptor protein 1 | 11326085[PMID] |
| PCSK9 | Disease-causing germline mutation(s) in | Assessed | HGNC:20001 | ENSG00000169174 | 607786 | 1p32.3 | proprotein convertase subtilisin/kexin type 9 | 24404629[PMID] |
Prevalence and incidence
6 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Annual incidence | 1-9 / 1 000 000 | 0.5842 / 100 000 | Japan | Value and class | Validated | 21146822[PMID] |
| Point prevalence | 1-9 / 1 000 000 | 0.3194 / 100 000 | Worldwide | Value and class | Validated | 31947532[PMID]_32439005[PMID]_ORPHANET |
| Point prevalence | 1-9 / 1 000 000 | 0.22 / 100 000 | Spain | Value and class | Validated | 27784735[PMID] |
| Point prevalence | 1-9 / 1 000 000 | 0.625 / 100 000 | Denmark | Value and class | Validated | 23956253[PMID] |
| Point prevalence | 1-9 / 1 000 000 | 0.33 / 100 000 | Netherlands | Value and class | Validated | 24585268[PMID] |
| Point prevalence | 1-9 / 1 000 000 | 0.125 / 100 000 | Germany | Value and class | Validated | 23662069[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
HPO phenotypes
33 annotations · validated 2017-02-27| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Obligate (100%) | ||
| HP:0003124 | Hypercholesterolemia | |
| HP:0003077 | Hyperlipidemia | |
| HP:0003141 | Increased LDL cholesterol concentration | |
| Very frequent (99-80%) | ||
| HP:0004416 | Precocious atherosclerosis | |
| HP:0005177 | Premature arteriosclerosis | |
| Frequent (79-30%) | ||
| HP:3000062 | Abnormal internal carotid artery morphology | |
| HP:0005162 | Abnormal left ventricular function | |
| HP:0100261 | Abnormal tendon morphology | |
| HP:0001681 | Angina pectoris | |
| HP:0012397 | Aortic atherosclerosis | |
| HP:0007201 | Cerebral artery atherosclerosis | |
| HP:0001677 | Coronaryartery atherosclerosis | |
| HP:0002094 | Dyspnea | |
| HP:0030148 | Heart murmur | |
| HP:0001397 | Hepatic steatosis | |
| HP:0000822 | Hypertension | |
| HP:0001658 | Myocardial infarction | |
| HP:0006693 | Myocardial steatosis | |
| HP:0004950 | Peripheral arterial stenosis | |
| HP:0005181 | Premature coronary artery atherosclerosis | |
| HP:0001920 | Renal artery stenosis | |
| HP:0001645 | Sudden cardiac death | |
| Occasional (29-5%) | ||
| HP:0002829 | Arthralgia | |
| HP:0004963 | Calcification of the aorta | |
| HP:0001653 | Mitral regurgitation | |
| HP:0000799 | Renal steatosis | |
| HP:0004381 | Supravalvular aortic stenosis | |
| HP:0010874 | Tendon xanthomatosis | |
| HP:0000991 | Xanthomatosis | |
| Very rare (<4-1%) | ||
| HP:0012373 | Abnormal eye physiology | |
| HP:0012638 | Abnormality of nervous system physiology | |
| HP:0030882 | Coronary artery aneurysm | |
| HP:0001138 | Optic neuropathy | |
Run the differential on the 5 obligate / very frequent terms
Annotation source: 4363406[PMID]_27462068[PMID]_25053660[PMID]_23759795[PMID]_19026292[PMID]_12750110[PMID]_6292899[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/391665
- This record as JSON: /data/d/391665.json