Suspected disorder | Gene(s) of interest | LipidSeq result | Diagnosis | Number of patients | Clinically relevant outcomes |
---|---|---|---|---|---|
HeFH | LDLR, APOB, PCSK9 | Heterozygous rare variant | HeFH | 623 | - Increased diagnostic certainty |
- Increased likelihood of third-party coverage for PCSK9 inhibitors | |||||
HoFH | LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA | Bi-allelic rare variants in either LDLR, APOB, PCSK9, or LDLRAP1 | HoFH | 8 | - Apheresis needs to be considered as a treatment |
- Higher intensity therapies enter the picture, including lomitapide and mipomersen | |||||
- Investigational treatments include AV8.TBG.hLDLR (RGX-501) gene therapy and anti-ANGPTL3 treatments (evinacumab or IONIS-ANGPTL3-LRx) | |||||
At least one non-null LDLR allele | HoFH | 3 | - A partial response to evolocumab is predicted | ||
Bi-allelic rare variants in ABCG5/ABCG8 | Sitosterolemia | 3 | - Change of clinical diagnosis from HoFH to sitosterolemia | ||
- Patients switched from standard HoFH treatment to a low plant diet and ezetimibe | |||||
Bi-allelic rare variants in LIPA | LALD, CESD or Wolman syndrome | 3 | - Change of clinical diagnosis from HoFH (or sometimes HeFH), usually in pediatric cases, to LALD [84] | ||
LALD | LIPA | Bi-allelic rare variants in LIPA | LALD, CESD or Wolman syndrome | 3 | - Diagnosed patients are eligible for sebelipase (infused lysosomal acid lipase replacement) |
ABL/FHBL | MTTP, APOB, SAR1B, PCSK9, ANGPTL3 | Bi-allelic rare variants in MTTP, APOB or SAR1B | ABL, homozygous FHBL or CRD, respectively | 6 | - Initiation of lifelong therapy to avert consequences of fat-soluble vitamin deficiencies |
- Fat restricted diet | |||||
- Additional clinical monitoring | |||||
Familial chylomicronemia syndrome | LPL, APOC2, APOA5, GPIHBP1, LMF1 | Bi-allelic rare variants in LPL, APOC2, APOA5, GPIHBP1, or LMF1 | Familial chylomicronemia syndrome | 70 | - Initiation of lifelong fat restricted diet |
- Potential novel or investigational treatments, such as anti-apo C-III treatments (volanesorsen in Europe or AKCEA-APOCIII-LRx); anti-ANGPTL3 treatments (evinacumab or IONIS-ANGPTL3-LRx) | |||||
Bi-allelic rare variants in APOC2 | APOC2 deficiency | 5 | - Potential for investigational apo C-II infusion | ||
Hypoalpha-lipoproteinemia | LCAT, APOA1, ABCA1 | Bi-allelic rare variants in LCAT | LCAT deficiency | 2 | - Monitoring of renal function |
- Potential for investigational LCAT infusion (ACP-501); | |||||
Bi-allelic rare variants in APOA1 or ABCA1 | Apo A-I deficiency or Tangier disease, respectively | 4 | - Potential for investigational apo A-I infusion (CSL-112) | ||
Lipodystrophy | LMNA, PPARG | Heterozygous variants in LMNA or PPARG | FPLD2 or FPLD3, respectively | 130 | - Increased monitoring for metabolic syndrome complications |
- Broad-spectrum CVD prevention initiated | |||||
- Possible leptin therapy | |||||
MODY | HNF1A, GCK | Heterozygous variants usually in HNF1A or GCK | MODY3 or MODY2, respectively | 110 | - Switch from insulin to diet and oral hypoglycemic agents particularly in MODY2 |