This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is Hepatic Lipase Deficiency (HLD)?
Hepatic Lipase Deficiency (HLD) is a rare genetic condition that usually presents with dyslipidemia, or increased levels of triacylglycerides or cholesterol in the blood. It is associated with an increased risk of developing coronary artery disease (atherosclerosis) and heart disease. Mutations, or changes, in the LIPC gene lead to the development of the condition. These changes can be transmitted in an autosomal recessive manner [1].
Symptoms of HLD
Hepatic lipase deficiency is normally characterized by increased levels of triglycerides and cholesterol in the blood. Affected persons may also display increased levels of high-density lipoproteins (HDLs) and decreased levels of low-density lipoproteins (LDLs). Diagnosis is based on many factors including, but not limited to, family history, patient medical history, symptoms, and laboratory testing. If you have questions about diagnosis please contact a medical professional [2]. |
Table 1. Desirable lipid levels in adult humans [3, 4].
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What causes Hepatic Lipase Deficiency?
Lipase C (LIPC) gene
Mutations in Lipase C lead to the development of hepatic lipase deficiency. LIPC encodes instructions to make the enzyme hepatic lipase (HL). Hepatic lipase normally converts very low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs) into low-density lipoproteins (LDLs) (Figure 1). It also helps transport high-density lipoproteins (HDLs) carrying cholesterol and triglycerides from the blood into the liver. Once in the liver, cholesterol and triglycerides are redistributed or removed from the body. In order to carry out these functions, hepatic lipase must be produced by liver cells and then secreted into the bloodstream. Mutations that lead to the development of HLD either prevent the release of hepatic lipase form the liver or decreases its enzymatic activity once in the bloodstream. This alters the lipid levels in an affected person’s bloodstream, causing abnormally high cholesterol and triglyceride levels [5].
Mutations in Lipase C lead to the development of hepatic lipase deficiency. LIPC encodes instructions to make the enzyme hepatic lipase (HL). Hepatic lipase normally converts very low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs) into low-density lipoproteins (LDLs) (Figure 1). It also helps transport high-density lipoproteins (HDLs) carrying cholesterol and triglycerides from the blood into the liver. Once in the liver, cholesterol and triglycerides are redistributed or removed from the body. In order to carry out these functions, hepatic lipase must be produced by liver cells and then secreted into the bloodstream. Mutations that lead to the development of HLD either prevent the release of hepatic lipase form the liver or decreases its enzymatic activity once in the bloodstream. This alters the lipid levels in an affected person’s bloodstream, causing abnormally high cholesterol and triglyceride levels [5].
Inheritance Pattern
Hepatic Lipase Deficiency (HLD) is inherited in an autosomal recessive manner. Autosomal means that the disease is associated with a chromosome other than the X or Y chromosomes. Recessive indicates that two mutated, or changed, copies of the gene are needed to cause the disease. The diagram on the left depicts a typical autosomal recessive inheritance pattern. Carriers are people who only have one copy of the mutated gene. If two carriers of the mutated LIPC gene have children, each of their children have a 25% chance of getting HLD [7]. |
Outcomes of Hepatic Lipase Deficiency
Coronary Artery Disease (CAD)
Hepatic lipase deficiency may be associated with an increased risk of developing coronary artery disease (CAD or atheroschlerosis). However, more research is needed to determine the long term effects of elevated triglycerides and cholesterol in the blood [2, 5]. |
What don't we know about Hepatic Lipase Deficiency?
Mouse studies have shown that deleting LIPC from the mouse genome results in lower reproductive potential. However, the effects of hepatic lipase deficiency mutations on reproductive potential has not been investigated.
More Information
References
[1] Connelly, P. W., & Hegele, R. A. (1998). Hepatic Lipase Deficiency. Critical Reviews in Clinical Laboratory Sciences,35(6), 547-572. doi:10.1080/10408369891234273
[2] Hepatic lipase deficiency. (n.d.). Retrieved February 3, 2019, from https://rarediseases.info.nih.gov/diseases/12864/hepatic-lipase-deficiency
[3] Can triglycerides affect my heart health? (2018, September 13). Retrieved February 3, 2019, from https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186
[4] High cholesterol. (2017, August 15). Retrieved February 3, 2019, from https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/diagnosis-treatment/drc-20350806
[5] Hepatic lipase deficiency - Genetics Home Reference - NIH. (n.d.). Retrieved February 3, 2019, from https://ghr.nlm.nih.gov/condition/hepatic-lipase-deficiency#resources
[6] Ng, D. M., Burnett, J. R., Bell, D. A., Hegele, R. A., & Hooper, A. J. (2019). Update on the diagnosis, treatment and management of rare genetic lipid disorders. Pathology, 51(2), 193-201. doi:10.1016/j.pathol.2018.11.005
[7] Autosomal recessive inheritance pattern. (n.d.). Retrieved February 3, 2019, from https://www.mayoclinic.org/autosomal-recessive-inheritance-pattern/img-20007457
[8] Wade, R. L., Andel, R. A., Rice, S. G., Banka, C. L., & Dyer, C. A. (2002). Hepatic Lipase Deficiency Attenuates Mouse Ovarian Progesterone Production Leading to Decreased Ovulation and Reduced Litter Size. Biology of Reproduction,66(4), 1076-1082. doi:10.1095/biolreprod66.4.1076
Non-linked Figures:
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[2] Hepatic lipase deficiency. (n.d.). Retrieved February 3, 2019, from https://rarediseases.info.nih.gov/diseases/12864/hepatic-lipase-deficiency
[3] Can triglycerides affect my heart health? (2018, September 13). Retrieved February 3, 2019, from https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186
[4] High cholesterol. (2017, August 15). Retrieved February 3, 2019, from https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/diagnosis-treatment/drc-20350806
[5] Hepatic lipase deficiency - Genetics Home Reference - NIH. (n.d.). Retrieved February 3, 2019, from https://ghr.nlm.nih.gov/condition/hepatic-lipase-deficiency#resources
[6] Ng, D. M., Burnett, J. R., Bell, D. A., Hegele, R. A., & Hooper, A. J. (2019). Update on the diagnosis, treatment and management of rare genetic lipid disorders. Pathology, 51(2), 193-201. doi:10.1016/j.pathol.2018.11.005
[7] Autosomal recessive inheritance pattern. (n.d.). Retrieved February 3, 2019, from https://www.mayoclinic.org/autosomal-recessive-inheritance-pattern/img-20007457
[8] Wade, R. L., Andel, R. A., Rice, S. G., Banka, C. L., & Dyer, C. A. (2002). Hepatic Lipase Deficiency Attenuates Mouse Ovarian Progesterone Production Leading to Decreased Ovulation and Reduced Litter Size. Biology of Reproduction,66(4), 1076-1082. doi:10.1095/biolreprod66.4.1076
Non-linked Figures:
Header