What is the pathophysiology of type I hyperlipoproteinemia (HLP)?

Updated: Jun 27, 2019
  • Author: Henry J Rohrs, III, MD; Chief Editor: Stuart Berger, MD  more...
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Answer

Type I HLP is present when the TGs are predominantly elevated. TG levels may exceed 1000-2000 mg/dL, and levels as high as 25,000 mg/dL have been observed. Type I HLP is also termed chylomicron syndrome or hyperchylomicronemia syndrome. In type I HLP, the plasma infranatant on standing is clear, whereas the supernatant is cloudy because of elevated chylomicrons that float to the top of the plasma. Supernatants form only when chylomicrons are present. The presence of chylomicrons is best confirmed by obtaining plasma lipoprotein ultracentrifugation, performed by a referral laboratory that specializes in lipid analysis. Lipoprotein electrophoresis (LPE) is far less quantitative than ultracentrifugation.

Most cases of type I HLP are caused by congenital deficiency of LPL, congenital deficiency of apoprotein C-II, or an LPL inhibitor (eg, an anti-LPL autoantibody). In healthy children and adults, chylomicrons are rapidly cleared from the circulation after a meal. When LPL or apoprotein C-II is deficient, chylomicrons can be detected for more than 12 hours after a meal. The normal half-life of chylomicrons in plasma is approximately 17 minutes. Because TGs are not being cleared at the tissue level (eg, TG is not released from the chylomicrons to muscle and adipose tissue) in type I HLP, most chylomicrons are taken up by the liver and spleen, resulting in hepatosplenomegaly, macrophage uptake (foam cell formation), and the development of cutaneous xanthomas.

If prolonged hypertriglyceridemia is untreated, eruptive xanthomas (discrete 1-mm to 6-mm papules) may appear on the extensor surfaces of the extremities. Lipemia retinalis may also occur. The retinal vessels appear white-to-yellow in color because of the striking hyperchylomicronemia.

When TG levels exceed 1000-2000 mg/dL, the risk of pancreatitis is increased. Infants may present with colicky abdominal pain and even failure to thrive. In older children, acute pancreatitis can cause tremendous pain, nausea, vomiting, and even death if undetected and untreated. Recurrent pancreatitis can be debilitating.

In one study of patients with LPL deficiency, 80% presented before age 10 years, with 30% presenting before age one. In contrast, apoprotein C-II deficiency is usually diagnosed later in life (>13 years). Apoprotein C-II deficiency rarely presents in infancy.

At least 40 molecular defects in LPL and 12 different molecular defects in apoprotein C-II have been reported. Both LPL and apoprotein C-II deficiencies are inherited as autosomal recessive traits and affect approximately 1 in 1 million persons in the general population. Because LPL and apoprotein C-II deficiencies are inherited as autosomal recessive traits, the family history is generally unrevealing, although some parents of children with LPL or apoprotein C-II deficiency have been cousins. Carriers of LPL mutations are asymptomatic.

Note that lipemic serum can interfere with many laboratory determinations, including enzyme activity measurements, antigen-antibody assays, and various spectrophotometric assays.


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