ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 12.15 | DOI: 10.1530/ey.18.12.15

J Med Biochem. 2020 Sep 2;39(3):283–289. doi: 10.2478/jomb-2019-0038. PMID: 33269016.

In brief: This case report serves as a platform to discuss the differential diagnosis of severe hypercholesterolemia. A young woman with T1DM and autoimmune liver disease presented with an LDL cholesterol value >1000 mg/dl (>26 mmol/l). She had no family history to suggest familial hypercholesterolemia. No mutations were identified in her LDLR, APOB and PCSK9 genes. Biochemical analysis showed elevated serum liver enzymes, which led to the detection of abnormal lipoprotein fraction, lipoprotein X (LpX), and prompted appropriate treatment, plasmapheresis.

Comment: Lipoprotein X has a similar density to LDL, making LpX cholesterol indistinguishable from LDL by conventional assay methods. Hence, LpX may be responsible for false elevations in LDL cholesterol. Rather, it is identified using lipoprotein electrophoresis, where LpX runs in a reversely migrating band. LpX is present in the plasma of patients affected by extra and intrahepatic cholestasis, in patients who receive lipid-rich parenteral nutrition, and rarely in lecithin-cholesterol-acyl-transferase deficiency. Cholestasis has been suggested to result in spillage of lipid fractions from bile into plasma, where they combine non-covalently with albumin to form LpX. LpX is rich in phospholipids, albumin and free cholesterol. However, unlike LDL, LpX has no apoB-100 and therefore should be suspected when unusually rapid elevations in LDL-C are encountered with a low apoB concentration.

Clinical studies have shown that cardiovascular disease risk is not increased by Lp-X (1). However, very high Lp-X concentrations may produce hyperviscosity syndrome. Treatment with statins, ezetimibe and PCSK9 inhibitors lack efficacy in reducing Lp-X. As LpX has no apoB, statins do not affect the removal of this lipoprotein by the liver. Furthermore, patients with cholestatic disease might reach toxic statin concentrations. Similarly, due to low levels of apoB, LDL apheresis is not recommended for LpX removal, as the absence of apoB reduces its effectiveness. Instead, plasmapheresis is the treatment for hyperviscosity syndrome due to high LpX.

Reference: 1. Fellin R, Manzato E. Lipoprotein-X fifty years after its original discovery. Nutrition, metabolism, and cardiovascular diseases: NMCD. 2019; 29(1): 4–8.

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