Information on the following diseases can be found in the Related Disorders section of this report:

• familial apolipoprotein C-II deficiency
• familial hepatic lipase deficiency

Familial LPL deficiency is characterized by an abnormally high blood concentration of droplets of a fatty substance called chylomicrons after eating fatty foods. Most people with familial LPL deficiency develop symptoms before ten years of age, however, some women do not have symptoms until pregnancy.

Approximately 50% of affected individuals develop skin lesions called eruptive xanthomas. These xanthomas are raised whitish-yellow colored skin nodules on a slightly red base. They vary in size from 0.1 to 0.3 inches in diameter, but are often clustered and may grow together to form larger plaques. The number of nodules may vary from a few to hundreds. They are usually located over the buttocks, shoulders, and extremities. However, lesions may be found on any site including the face and mucous membranes. Eruptive xanthomas are neither painful nor itchy. They usually appear within a few days after triglyceride levels in the blood plasma have begun to increase. They contain a yellowish greasy substance and sometimes a milky fluid. They disappear again when the increased fat in blood plasma (lipemia) starts to vanish. Only a slight discoloration finally remains.

Episodes of abdominal pain are common. Intensity, duration, and localization of episodes are variable. The attacks may be associated with lack of appetite (anorexia), nausea, abdominal distension, fever, and diarrhea. Some patients with the disorder may not experience abdominal pain. Inflammation of the pancreas, sometimes with bleeding, often occurs when triglyceride levels are excessively high. Enlargement of the liver and spleen occurs particularly among affected infants and children. The enlargement of these organs may vary, often in parallel with the fat content of the diet. Large cells that swallow other cell material (macrophages) that have incorporated chylomicrons often appear in the spleen and sometimes in bone marrow of these patients.

In the presence of excessive fatty substances in the blood (hyperlipemia) the arteries and veins in the outer parts of the eye's retina have a milky or tomato juice appearance. The back of the eyeball (fundus) may appear pale pink upon examination by an ophthalmologist. The change is related to the degree of lipemia. The retina may contain white fatty deposits. Blood circulation in the retina may also become disturbed, and narrowing of the blood vessels and bleeding may occasionally occur. These symptoms are reversible and do not affect the vision of individuals with familial LPL deficiency.

Familial lipoprotein lipase deficiency is caused by a mutation in the LPL gene leading to very low or absent activity of the lipoprotein lipase enzyme. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

LPL deficiency is inherited as an autosomal recessive genetic trait. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Familial LPL deficiency occurs in approximately one per million people in the general population. Some areas of Quebec, Canada have been found to have a higher prevalence.

Familial LPL deficiency occurs in all races and affects males and females in equal numbers.

Symptoms of the following disorders are similar to those of familial LPL deficiency. Comparisons may be useful for a differential diagnosis:

Familial apolipoprotein C-II deficiency is a rare autosomal recessive genetic disorder. It is characterized by a deficiency of apolipoprotein C-II, a factor needed for functioning of the enzyme lipoprotein lipase, causing an accumulation of chylomicrons and very low-density lipoproteins (VLDL) in blood plasma. Recurrent attacks of pancreas infection (pancreatitis) may also occur as well as insulin dependent diabetes mellitus. Symptoms usually develop later in life (age-13-60) than with familial LPL deficiency.

Familial hepatic lipase deficiency is a rare autosomal recessive genetic disorder characterized by elevated levels of triglycerides and early-onset coronary artery disease.

Diagnosis
Familial LPL deficiency is diagnosed when the activity of the lipoprotein lipase enzyme in blood plasma is very low or absent following intravenous administration of heparin. The accumulation of triglycerides causes the blood plasma to have a milky appearance. Molecular genetic testing for mutations in the LPL gene is available for genetic counseling purposes.

Treatment
Restriction of fat in the diet is the most effective treatment for familial LPL deficiency. Eruptive xanthomas that recur or do not resolve may indicate that treatment is not adequate. Affected individuals should avoid the use of alcohol and drugs that can increase triglyceride concentration such as estrogens, diuretics, isotretinoin, Zoloft and beta-adrenergic blocking agents. During pregnancy, women with familial LPL deficiency need strict dietary control and monitoring of blood triglyceride levels.

Genetic counseling is recommended for families with a child diagnosed with familial LPL deficiency.

Research is underway to determine if gene therapy is feasible as a treatment for familial LPL deficiency.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Brunzell JD. (Updated 4/9/04). Familial Lipoprotein Lipase Deficiency. In: GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2005. Available at http://www.genetests.org. Accessed 4/05.

Demaker PNM and Stalenhoef AFH. Familial Lipoprotein Lipase Deficiency. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003: 465-66.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 238660: Last Update:2/4/05.

Brunzell JD. Familial lipoprotein lipase deficiency and other causes of chylomicronemia syndrome. In: Scriver CR, Beaudet AL, Sly WS et al., eds. The metabolic basis of inherited disease. Vol. 2. New York: McGraw-Hill, 1995:1913-1927.

Brunzell JD, Deeb SS. Familial lipoprotein lipase deficiency, apo CII deficiency and hepatic lipase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease, 8th ed. McGraw-Hill, New York, 2001:2789-816.

Gilbert B, Rouis M, Griglio S, DeLumley L, Laplaud P. Lipoprotein lipase (LPL) deficiency: a new patient homozygote for the preponderant mutation Gly188Glu in the human LPL gene and review of reported mutation: 75% are clustered in exons 5 and 6. Ann Genet 2001;44:25-32.