Table 4.
Selected clinical outcomes using the results from the LipidSeq panel
| 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 |
Abbreviations: ABL abetalipoproteinemia, CESD cholesteryl ester storage disease, CRD chylomicron retention disease, CVD cardiovascular disease, FHBL hypobetalipoproteinemia, FPLD familial partial lipodystrophy, HeFH heterozygous familial hypercholesterolemia, HoFH homozygous familial hypercholesterolemia, LALD lysosomal acid lipase deficiency, MODY maturity-onset diabetes of the young