Hepatic lipase deficiency is a disorder that affects the body's ability to break down fats (lipids). People with this disorder have increased amounts of certain fats, known as triglycerides and cholesterol, in the blood. These individuals also have increased amounts of molecules known as high-density lipoproteins (HDLs) and decreased amounts of molecules called low-density lipoproteins (LDL). These molecules transport triglycerides and cholesterol throughout the body. In people with hepatic lipase deficiency, the LDL molecules are often abnormally large.

Normally, high levels of HDL (known as "good cholesterol") and low levels of LDL (known as "bad cholesterol") are protective against an accumulation of fatty deposits on the artery walls (atherosclerosis) and heart disease. However, some individuals with hepatic lipase deficiency, who have this imbalance of HDL and LDL, develop atherosclerosis and heart disease in mid-adulthood, while others do not. It is unknown whether people with hepatic lipase deficiency have a greater risk of developing atherosclerosis or heart disease than individuals in the general population. Similarly, it is unclear how increased blood triglycerides and cholesterol levels affect the risk of atherosclerosis and heart disease in people with hepatic lipase deficiency.

Hepatic lipase deficiency is caused by mutations in the LIPC gene. This gene provides instructions for making an enzyme called hepatic lipase. This enzyme is produced by liver cells and released into the bloodstream where it helps convert very low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs) to LDLs. The enzyme also assists in transporting HDLs that carry cholesterol and triglycerides from the blood to the liver, where the HDLs deposit these fats so they can be redistributed to other tissues or removed from the body.

LIPC gene mutations prevent the release of hepatic lipase from the liver or decrease the enzyme's activity in the bloodstream. As a result, VLDLs and IDLs are not efficiently converted into LDLs, and HDLs carrying cholesterol and triglycerides remain in the bloodstream. It is unclear what effect this change in lipid levels has on people with hepatic lipase deficiency.

Normal Function

The LIPC gene provides instructions for making an enzyme called hepatic lipase. This enzyme is produced by liver cells and released into the bloodstream where it helps with the conversion of fat-transporting molecules called very low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs) to low-density lipoproteins (LDLs). The enzyme also assists in transporting molecules called high-density lipoproteins (HDLs) that carry cholesterol and triglycerides from the blood to the liver, where the HDLs deposit these fats so they can be redistributed to other tissues or removed from the body. Hepatic lipase helps to keep these fat-transporting molecules in balance by regulating the formation of LDLs and the transport of HDLs. Normally, high levels of HDL (known as "good cholesterol") and low levels of LDL (known as "bad cholesterol") are protective against heart disease.

Health Conditions Related to Genetic Changes

Hepatic lipase deficiency

At least 10 mutations in the LIPC gene have been found to cause hepatic lipase deficiency. This condition leads to abnormal levels of various fats (lipids) in the bloodstream, although it is unclear whether these changes impact the risk of developing heart disease. The LIPC gene mutations that cause this condition change single protein building blocks (amino acids) in the hepatic lipase enzyme. These mutations prevent the enzyme's release from the liver or decrease its activity in the bloodstream. As a result, VLDLs and IDLs are not efficiently converted into LDLs, and HDLs carrying cholesterol and triglycerides remain in the bloodstream. It is unclear what effect this change in fat levels has on people with hepatic lipase deficiency, as some affected people develop an accumulation of fatty deposits on the artery walls (atherosclerosis) and heart disease in mid-adulthood, while others do not.

Age-related macular degeneration

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Other Names for This Gene

• HDLCQ12
• hepatic lipase
• HL
• HTGL
• lipase C, hepatic
• lipase member C
• lipase, hepatic
• LIPH

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Hepatic lipase deficiency is likely a rare disorder; only a few affected families have been reported in the scientific literature.