Definitive diagnosis of familial chylomicronemia requires special tests.  The signs and symptoms of the disease overlap with those of other conditions, and some patients may not be diagnosed for many years.  Other genetic diseases cause recurrent pancreatitis, and others still cause hepatosplenomegaly.  The condition may also at first be confused with other closely related conditions that involve altered levels of fats in the bloodstream, other dyslipidemias.  An accurate diagnosis is essential for proper management of the disease.

Diagnosis begins with the assessment of the patient’s symptoms and clinical course, as well as their clinical exam, noting the symptoms described previously.  The physician utilizes lab values as well.  When an individual first starts to show symptoms, a wide variety of tests may be performed to zone in on the possible causes of the condition.  For example, a colicky infant who is failing to gain weight normally might first have a basic workup performed using blood to test for anemia, infection, and kidney and liver problems.  An individual with pancreatitis might be evaluated with similar basic blood tests, as well as for amylase and lipase levels, which are usually elevated in pancreatitis.  (However, amylase levels are sometimes deceptively normal during pancreatitis in these patients, as the triglycerides in the blood can disrupt the test.)

High triglycerides from various causes are a relatively common cause of pancreatitis; thus the extremely high level triglycerides found in the condition may be noted at the initial work-up if pancreatitis is diagnosed.  Triglycerides are usually greater than 1000 mg/dL.  (Greater than 200 is considered high and over 500 is considered very high.)   Due to the high level of triglycerides and chylomicrons, blood plasma collected from these patients may appear milky white instead of watery when spun in a laboratory machine.   Cholesterol levels are non diagnostic.  Very-low-density lipoproteins (VLDLs) are reduced or normal in lipoprotein lipase deficiency, but may be somewhat elevated in cases of apolipoprotein-CII deficiency.

Imaging such as CT scans or ultrasounds may be performed to evaluate abdominal pain and pancreatitis or to assess hepatosplenomegaly.  Sometimes a xanthoma is biopsied to rule out other dermatological conditions.

In one important test, technicians measure the activity level of lipoprotein lipase (LPL) in the bloodstream.  Heparin, a drug that decreases the blood’s clotting ability, is injected into a vein.  This releases lipoprotein lipase from the lining of the blood vessels.  The blood sample is taken, and the amount of LPL activity is measured: low or absent activity is expected in the condition.  This test can also be performed on a piece of biopsied adipose (fat) tissue.  In either case, the test does not distinguish between those with a defect in apolipoprotein C-II and those with a mutation in lipoprotein lipase itself.  Apolipoprotein C-II level may then be assessed by the lab technique of gel electrophoresis; it is reduced in those with a defect in apolipoprotein C-II.

Genetic analysis provides the definitive diagnosis.  The patient donates a sample of blood or saliva.  Technicians then isolate the patient’s DNA and examine the LPL gene or the apolipoprotein C-II gene for mutations.  Genetic testing can be performed on other family members as well to see if they have the condition or are carriers for it.  Brothers and sisters of someone with condition have a 25% chance of having the disease and a 50% chance of being a carrier with a single defective gene.  People with a single defective gene do not have the disease, but if they have a child with another person with a defective gene, they have a one in four chance of having a child with the disorder.