CASE FILES: BIOCHEMISTRY
than apoE3 and chylomicron remnants and VLDL remnants containing apoE2
are cleared more slowly from the circulation.
The most common genetic defect leading to hypertriglyceridemia is a defi-
ciency in LPL, which results in increased levels of both chylomicrons and
VLDL. Individuals who are homozygous for the defective gene usually pres-
ent with symptoms of chylomicronemia (TG levels >2000 mg/dL, abdominal
pain, pancreatitis, xanthomas,
in childhood. Clinical diagno-
sis of LPL deficiency requires measurement of LPL activity in plasma follow-
ing intravenous injection of heparin, which displaces the LPL from its heparan
sulfate tether. However, heparin also releases HL into the plasma and the
post-heparin plasma must be treated with antibodies specific to HL to remove it.
Alternatively, LPL can also be measured in adipose tissue, which has no HL
activity. A deficiency in apoC-II will also show evidence of decreased pos-
theparin plasma LPL activity. An increase in LPL activity when normal apoC-II
is added to the assay indicates that a defect in apoC-II is the culprit.
A deficiency in HL can also lead to elevated plasma TG levels, however,
these increases in TG are usually found in VLDL remnants, LDL, and HDL,
which all become more buoyant in their densities. Definitive diagnosis of HL
deficiency is made by demonstrating the absence of HL activity in postheparin
C O M P R E H E N SIO N Q U E ST IO N S
[35.1] A teenage boy presents with moderate to severe epigastric pain.
Physical examination reveals extensive eruptive xanthomas and
hepatosplenomegaly. A blood sample reveals milky plasma. Which of
the following is the most likely lipoprotein to be elevated in this
B. Chylomicron remnants
[35.2] Laboratory results for a patient with uncontrolled Type I diabetes
mellitus reveal hyperglycemia (634 mg/dL) and hypertriglyceridemia
(498 mg/dL). The most likely cause of the hypertriglyceridemia in this
patient is which of the following?
A. Deficiency in apoprotein C-II
B. Increased hepatic triglyceride synthesis
C. Decreased lipoprotein lipase activity
D. Deficiency in LDL receptors
E. Absence of hormone-sensitive lipase