At a Glance

Familial apolipoprotein CII deficiency is a very rare (rarer than LPL deficiency) autosomal recessive disorder in which apolipoprotein CII (apoC-II), a cofactor for LPL, is absent, the clearance of chylomicrons from the blood is greatly impaired and triglycerides (TG) accumulate in the plasma. Very low-density lipoproteins (VLDL) may also be elevated.

Because apoC-II deficiency results in the functional deficiency of LPL, it has very similar clinical manifestations to primary LPL deficiency and is diagnosed in children and adults on the basis of recurrent abdominal pain, attacks of pancreatitis and/or detection of milky fasting plasma. However, interesting phenotypic differences exist. The homozygous apoC-II deficient patient is usually detected later, between 13 and 60 years of age, although symptoms may be traced back to childhood. Patients with apoC-II deficiency tend not to have xanthomas or hepatosplenomegaly as often as those with LPL deficiency.

The later onset of symptoms (and higher dietary fat tolerance) in apoC-II deficiency might be due to a less severe defect in the clearance of chylomicrons and VLDL, as some residual LPL activity might exist. As in LPL deficiency, there is little evidence for atherosclerosis in individuals with apoC-II deficiency.

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What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Diagnosis is based on assay of LPL activity in postheparin plasma. Once apoC-II is added to the assay, the decrease in postheparin lipolytic activity corrects to normal. Deficiency of apoC-II can also be verified by gel electrophoresis of the apolipoproteins contained in VLDL and chylomicrons on 2D gels.

Test Results Indicative of the Disorder

Homozygous apoC-II deficient patients may have markedly elevated fasting plasma TG levels ranging from 500-10,000 mg/dL. Most of the TG is in the form of chylomicrons but there is an increase in VLDL-TG. VLDL cholesterol (VLDL-C) levels are above normal, whereas LDL-C and HDL-C are very low, similar to that seen in LPL deficiency. Immunoassays may reveal low plasma levels of apoA-1, apoA-II, and apoB and high concentrations of apoC-III and apoE in these patients.

Individuals hetrozygous for a defective APOC2 mutation have normal plasma lipid levels.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Secondary causes of hypertriglyceridemia include diabetes, alcohol intake, hypothyroidism, renal failure, glucocorticoid, or any of several pharmaceutical agents (e.g., sertraline, beta-blockers, certain hypertensive agents, estrogen therapy, and HIV protease inhibitors).

What Lab Results Are Absolutely Confirmatory?

The definitive diagnosis of apoC-II deficiency is often confirmed by genetic analysis in probands and family members. More than 10 structural defects in the APOC2 gene have been associated with, in the homozygous state, the absence of apoC-II or production of defective apoC-II.

Heterozygotes have a 50% reduction in apoC-II levels but normal lipid levels.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Familial apoC-II deficiency should be considered in patients with marked fasting triglyceride elevations without known secondary causes of hypertriglyceridemia. Diagnosis can be determined by performing LPL activity analysis in postheparin plasma. If LPL activity is diminished, it points to primary LPL deficiency or co-factor (apoC-II) deficiency. Recovery of LPL activity in plasma after addition of apoC-II to the sample points to an apoC-II deficiency.