The Skinny on Fat
CP case conference
February 2012
Patient presentation
18 y/o Iraqi female
1 prior episode of chest pain
No angina or dyspnea on exertion
Eruptive cutaneous
xanthomas on:
Elbows and olecranon
processes
Knees
Achilles tendons
Hand MCP joints
Patient presentation
In Syria:
Total cholesterol: 630
Triglycerides: 120
Started on Simvastatin and niacin
Total cholesterol: 603
HDL: 33, TRIG: 74, LDL: 555
Here, lipid panel showed:
Total cholesterol:713
HDL: 40, TRIG: 80, LDL: 657
Causes of hyperlipidemia
Clinical
classification
based on lipid
levels and
physical findings
Prevalence of
1/500 (!!)
Causes of hyperlipidemia
Defect may be in each component:
Apolipoproteins
around lipids droplets
LDL receptor – prevents docking of LDL droplet
LDLRAP1 – prevents binding of LDLR
Clathrin – prevents invagination
Apolipoprotein – prevents interaction with LDLR
Causes of hyperlipidemia
~1000 known mutations
Autosomal inheritance pattern
Dose-dependent impact on lipid levels
Variable effect by various mutations (not
entirely predicted by type of mutation)
Causes of hyperlipidemia
• Multiple mutations in LDLRAP1
Apolipoprotein E typing
Apolipoprotein E – component of LDL
recognized by the LDLR for uptake in the liver
3 isotypes – 2, 3, and 4
3.7kb gene located on chromosome 19
E2/E2 is associated with hyperlipidemia
E4 isoform is associated with Alzheimer dx
Apolipoprotein E typing
PCR amplification of the ApoE gene
Restriction digest with endonuclease CfoI
Differential
restriction band
pattern due to
changes in
recognition
sequence
Pt is E3/E3
Treatment Options
Medications:
Statins
Cholesterol binding resins
Surgery:
Ileal bypass surgery
Portocaval anastomosis
Liver transplantation
LDL pheresis
Lipid pheresis
Lipid pheresis
video
Lipid pheresis
Effect on our patient
• Lipid levels since initiating pheresis
Effect on our patient
date
Total Chol
6/18/2010
337
6/18/2010
114
7/2/2010
269
7/2/2010
90
7/8/2011
189
7/8/2011
64
date
6/18/2010
6/18/2010
7/2/2010
7/2/2010
7/8/2011
7/8/2011
Total Chol % change
337
114
269
90
189
64
66%
67%
66%
TRIG
57
28
79
24
73
26
TRIG
57
28
79
24
73
26
HDL
35
23
32
21
25
19
% change
HDL
51%
70%
64%
35
23
32
21
25
19
LDL
291
84
222
65
228
40
% change
34%
34%
24%
LDL
291
84
222
65
228
40
% change
71%
71%
82%
Questions?