The Skinny on Fat

1. The Skinny on Fat CP case conference February 2012

2. 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

3. 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

4. Causes of hyperlipidemia • Clinical classification based on lipid levels and physical findings • Prevalence of 1/500 (!!)

5. Causes of hyperlipidemia • Defect may be in each component: • LDL receptor – prevents docking of LDL droplet • LDLRAP1 – prevents binding of LDLR • Clathrin – prevents invagination • Apolipoprotein – prevents interaction with LDLR Apolipoproteins around lipids droplets

6. 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)

7. Causes of hyperlipidemia • Multiple mutations in LDLRAP1

8. 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

9. 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

10. Treatment Options • Medications: • Statins • Cholesterol binding resins • Surgery: • Ileal bypass surgery • Portocaval anastomosis • Liver transplantation • LDL pheresis

11. Lipid pheresis

12. Lipid pheresis video

13. Lipid pheresis

14. Effect on our patient • Lipid levels since initiating pheresis

15. Effect on our patient

16. Questions?