More detailed biochemistry and background

Familial chymomiconemia syndrome is not the only condition that presents with chlomicronemia with severe hypertriglyceridemia.  Certain extremely rare genetic disorders can also cause this presentation, including familial apoAV deficiency, familial lipase maturation factor 1 deficiency, and familial GPIHDLBP1 deficiency.

Traditionally, dyslipidemias have been classified by patterns of elevation in lipids and lipoproteins.  Elevated chylomicrons also occur in cases of type V hyperlipoproteinemia (also called mixed hyperlipidemia).  This disorder causes elevated VLDLs and cholesterol as well as elevated chylomicrons.  The disorder occurs in about 1 in 600 persons.  Unlike familial chylomicronemia syndrome, it results from the interactions of several genes with contribution from several environmental factors such as diabetes and excessive alcohol use.   Type II hyperlipoproteinmia is characterized by elevations in Low-density lipoproteins (LDLs) and cholesterol.  In type III, VLDLs, chylomicrons remnants, triglycerides, and cholesterol are all elevated.   Type IV is marked by elevations in VLDLs and triglycerides.

Dyslipidemias are also characterized as primary or secondary.  In a primary dyslipidemia, such as familial chylomicronemia syndrome, a genetic mutation causes the dyslipidemia.  In secondary dyslipidemias, other environmental causes or diseases contribute to the abnormal lipid patterns.  The former cause only a small percentage of dyslipidemia cases in adults, though they are the most common cause of dyslipidemias in children.   The most common secondary cause in developed countries is a diet with excess saturated fat, cholesterol, and trans fats in combination with insufficient exercise.  Other important secondary causes include excessive alcohol use, diabetes mellitus, renal insufficiency, hypothyroidism, cholestatic liver diseases, and certain drugs.  These include thiazide diuretics, beta-blockers, retinoids, HIV protease inhibitors, estrogens, and glucocorticoids.  Individuals with familial chylomicronemia syndrome need to be careful to avoid exacerbation of their symptoms which might occur from any of these secondary causes.  This includes management of secondary conditions and avoidance of these drugs.

The LPL gene is found on chromosome 8.  Nearly 100 gene mutations of this gene have been found to date.  Individuals with the condition often do not have exactly the same mutation on both of their malfunctioning genes—in other words, they are compound heterozygotes, though they are homozygous for the disease condition.

Carriers of these malfunctioning genes have one malfunctioning copy of the gene and one good copy.  These individuals, heterozygotes for the disease, demonstrate a fifty percent decrease in lipoprotein lipase activity.  Though these individuals do not manifest the symptoms of familial chylomicronemia syndrome, some note slightly increased triglycerides, especially with increasing age.  Their triglyceride levels remain much lower than those of homozygotes, but they may exacerbate an existing secondary hyperlipidemia.  For this reason and others, genetic testing may be advisable for suspected heterozygotes as well.