Test Code 890
Test Details
LipidSeq™
The LipidSeq test is a complete 23-gene sequencing panel aimed at identifying the genetic cause for specific lipid and lipoprotein disorders, which can be associated with premature cardiovascular disease, pancreatitis, kidney disease, or neurologic disease.
Methodology
Next Generation Sequencing
Patient Preparation
None
Preferred Specimen
2 mL saliva collected using the LipidSeq specimen kit.
Alternate Specimen
None
Transport Temperature
Room temperature
Stability
6 months at room temperature
Lab Values
LipidSeq™
LipidSeq evaluates the genetic cause of six major categories of biochemical abnormalities, each associated with several genetic disorders.
- Hypercholesterolemia–where direct LDL-C is ≥190 mg/dL.
- Elevated Sterols–disorders of sterol metabolism where ß-sitosterol is ≥10 mg/L or cholestanol is ≥10 mg/L.
- Hypertriglyceridemia–where fasting triglyceride values are ≥ 500 mg/dL.
- HDL Deficiency–where HDL-C is <25 mg/dL if male and <30 mg/dL if female.
- Hypocholesterolemia–where direct LDL-C is <10 mg/dL.
- HDL Excess–where there is established heart disease and HDL-C is ≥100 mg/dL if male and ≥120 mg/dL if female.
The genetic test will yield results categorized as positive, negative, or variant of uncertain significance.
Clinical Significance
LipidSeq™
| Biochemical Abnormality | Gene | Associated Conditions1-10 |
|---|---|---|
| Hypercholesterolemia | LDLR, APOB, PCSK9, STAP1, LDLRAP1, LIPA | Familial Hypercholesterolemia (FH), Lysosomal Acid Lipase Deficiency |
| HDL Deficiency | ABCA1, APOA1, LCAT | Tangier Disease, ApoA-1 Deficiency or variants, Familial LCAT Deficiency, Fish-Eye Deficiency |
| Elevated Sterols | ABCG5, ABCG8, CYP27A1 | Sitosterolemia, Cerebrotendinous Xanthomatosis (CTX) |
| Hypertriglyceridemia | LPL, APOC2, GPIHBP1, APOA5, APOE | Familial Hypertriglyceridemia, Dysbetalipoproteinemia |
| Hypocholesterolemia | APOB, MTTP, LIPG | Hypobetalipoproteinemia, Abetalipoproteinemia |
| HDL Excess | CETP, LIPC, APOC3, SCARB1 | CETP Deficiency, Hepatic Lipase Deficiency, APOC3 Deficiency, SCARB1 Deficiency |
References:
- Johansen CT et al. J Lipid Res. 2014; 55:765-772
- Schaefer EJ, Geller AS, Endress G. Current Opin Lipidology 2019;30:56-62.
- Sturm AC, Knowles JW, Gidding SS, et al. J Am Coll Cardiol. 2018;72:662-680.
- Corral P, Geller AS, Polisecki EY, et al. Atherosclerosis 2018;277:256-261.
- Khera AV, Won HH, Peloso GM, et al. J Am Coll Cardiol. 2016;67:2578-89.
- Geller AS, Polisecki EY, Diffenderfer MR et al. J Lipid Res. 2018;59:2421-2435.
- Schaefer EJ, Anthanont P, Diffenderfer MR, et al. Prog Cardiovasc Dis. 2016;59:97-106.
- Chyzhyk V, Kozmic S, Brown AS, et al. J Clin Lipidol. 2019;13:89-99.
- Brinton EA, Hopkins PN, Hegele RA, et al. J Clin Lipidol. 2018;12:152-161.
- Duell PB, Salen G, Eichler FS, et al. J Clin Lipidol. 2018;12:1169-1178.
Treatment Options
LipidSeq™
| Condition | Treatment |
|---|---|
| Extreme Hypertriglyceridemia | The goal of therapy is to reduce fasting triglyceride levels to <150 mg/dL, using dietary fat and sugar restriction, fenofibrate therapy (200 mg/day), omega-3 fatty acids supplementation (3 capsules twice daily), and, if necessary, statin therapy which will not only lower triglycerides but also optimize LDL-C levels. Optimization of diabetes control is also critical if diabetes is present. |
| Dysbetalipoproteinemia | The goal of therapy is to reduce fasting triglyceride levels to <150 mg/dL, using dietary fat and sugar restriction, fenofibrate therapy (200 mg/day), omega-3 fatty acids (3 capsules twice daily), and, if necessary, statin therapy which will not only lower triglycerides but also optimize RLP-C and LDL-C levels. Optimization of diabetes control is also critical if diabetes is present. |
| Sitosterolemia | Restriction of dietary cholesterol and plant sterols and treatment with ezetimibe and statins can prevent early ASCVD.5 Patients with heterozygous ABCG5 and ABCG8 defects may have a milder form of the disease. |
| Cerebrotendinous Xanthomatosis (CTX) | CDCA therapy, 250 mg given orally three times daily, can prevent the neurologic disease, provided the diagnosis is made early, ideally prior to age 30 years. |
| Familial Hypercholesterolemia (FH) | With early detection and treatment with effective statins, ezetimibe, and, if necessary, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, ASCVD can be prevented; and these patients can have a normal lifespan.3,7 Those patients that do not respond to statins, ezetimibe, anion-exchange resins, and/or PCSK9 inhibitors may require incliseran and/or LDL apheresis. |
| Lysosomal Acid Lipase Deficiency | If not diagnosed and treated with enzyme replacement (now available and known as sebelipase), the patient will develop liver failure. |
| Apolipoprotein A-I Deficiency | The treatment of choice is statin therapy to optimize LDL-C to < 50 mg/dL. |
| Tangier Disease | The treatment of choice is statin therapy to optimize LDL-C to <50 mg/dL. |
| LCAT Deficiency | The therapy of choice is to optimize the kidney disease risk factors: lower blood glucose levels and blood pressure and monitor kidney function. |
| Fish-Eye Disease | LDL-C levels should be optimized with lifestyle and statin treatment. |
| Hepatic Lipase Deficiency | The treatment of choice is to optimize triglyceride and LDL-C levels with fenofibrate, omega-3 fatty acids, and statins. |
| Hypobetalipoproteinmemia | Supplementation with fat soluble vitamins, co-enzyme Q10 (300 mg/day), and omega-3 fatty acids (4 grams/day) will prevent the muscle aches and other symptoms that these patients often have. |
| Abetalipoproteinemia | Supplementation with co-enzyme Q10, all the fat-soluble vitamins (A, D, E, and K), and omega-3 fatty acids (fish oil capsules, 4 grams/day) will often prevent the complications of this disease. Treatment with vitamin E, at least 800 units per day, is essential to prevent the neurologic disease that these patients develop. |
