AUTHOR=Kayikcioglu Meral , Ozkan Hasan Selcuk , Yagmur Burcu , Bayraktaroglu Selen , Vardarli Asli Tetik 

TITLE=Case report: Therapy adherence, MTTP variants, and course of atheroma in two patients with HoFH on low-dose, long-term lomitapide therapy

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1087089

DOI=10.3389/fgene.2022.1087089

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Homozygous familial hypercholesterolemia (HoFH) is a rare and devastating genetic condition characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) leading to an increased risk of premature atherosclerosis. Patients with Homozygous familial hypercholesterolemia mostly present with mutations in <italic>LDLR</italic>; however, herein, we present two cases with concomitant <italic>microsomal triglyceride transfer protein</italic> mutations, who showed different clinical courses and treatment adherence on long-term therapy with the new MTTP inhibitor lomitapide.</p><p><bold>Objectives:</bold> We aimed to present the possibility of preventing the progression of atherosclerotic burden with effective and safe LDL-C reduction in patients with Homozygous familial hypercholesterolemia on low-dose lomitapide therapy and emphasize the role of treatment adherence in therapy success.</p><p><bold>Methods:</bold> We present two patients with phenotypically Homozygous familial hypercholesterolemia, a compound heterozygous woman and a simple homozygous man, both with <italic>LDLR</italic> and additional <italic>MTTP</italic> mutations, who were treated with the MTTP-inhibiting agent lomitapide, with different treatment compliances. The role of impulsivity was investigated through <italic>Barratt Impulsivity Scale 11</italic>, and the extent of the atherosclerotic burden was followed up using coronary artery calcium scoring, echocardiographic and sonographic findings, and, eventually, through a strict follow-up of laboratory parameters. The patients were on lomitapide for 8 and 5 years, respectively, with no adverse effects.</p><p><bold>Conclusion:</bold> When accompanied by good adherence to therapy, low-dose lomitapide on top of standard lipid-lowering therapy with decreased frequency of lipid apheresis prevented the progression of atherosclerotic burden. Non-compliance might occur due to patient impulsivity and non-adherence to a low-fat diet.</p>