Massive tissue deposition of cholesterol leading to multi-organ failure in cholestatic hypercholesterolemia

Cholestasis-induced severe hypercholesteremia can result in various complications, including the development of xanthomas and concern that marked hypercholesterolemia may accelerate atherosclerosis. However, deposition of lipids and cholesterol in organs beyond the skin and tendons, to the extent that they induce organ dysfunction or organ failure, has not previously been reported. Here we present two cases of marked hypercholesterolemia resulting from hepatobiliary dysfunction and cholestasis. In one of the two individuals (patient 1) who presented to us at a later stage of disease progression than patient 2, massive cholesterol tissue deposition in the retina, myocardium and kidney resulted in profound vision loss and ultimately fatal cardiorenal failure, whereas the second individual (patient 2) was noted to have retinal cholesterol deposition with minimal vision loss but extensive, pruritic and painful, tuberoeruptive xanthomas. Both patients were placed on weekly or biweekly plasmapheresis to prevent further disease progression, which successfully lowered cholesterol from 62.2 to 6.92 mmol/L in patient 1 and 18.4 to 5.88 mmol/L in patient 2, respectively. Unfortunately, the massive tissue lipid deposition in patient 1 proved to be beyond recuperation for plasma exchange therapy. In contrast, six months of biweekly plasmapheresis in patient 2 yielded marked resolution of xanthomas and halted progression of retinal cholesterol deposition and vision loss. These cases highlight the importance of thorough, systemic examination in patients with severe hypercholesterolemia secondary to cholestatic liver disease and attention to the potential devastating impact of massive cholesterol tissue-deposition, beyond atherosclerosis, which can be ameliorated if detected early by frequent plasma exchange. • Marked hypercholesterolemia can cause fatal end-organ lipid deposition • Lipoprotein X can be diagnosed under clinical suspicion and abnormal serum markers • Plasmapheresis can be utilized to manage symptoms and reverse disease progression