👤 Francesco Sbrana

To date, despite the new lipid-lowering drugs, some subjects do not reach LDL-cholesterol and/or lipoprotein(a) [Lp(a)] goals and lipoprotein apheresis (LA) plays a role in atherosclerosis prevention. The aim of this study is to paint a portrait of the current LA activity in Italy, collecting data via an electronic survey. Forty-seven centers were contacted, data from 142 patients (male 67%) were obtained from 15 sites. Two sites had discontinued LA treatment. In the active sites, a median of 17 [14-26] LA treatment/patient per year was performed; 7/13 sites used more than one LA system, with venous vascular access used in 87% of cases. High Lp(a) plasma concentrations (> 60 mg/dL or ≥ 145 nmol/L) were recorded in 73/142 patients; 14/36 homozygous familial hypercholesterolemia patients were on lomitapide or evinacumab therapy. The PORTRAIT survey would like to promote a network to better manage the patients on chronic LA. Show less

Familial hypercholesterolemia (FH) is less rare than one might think and, despite highly effective lipid-lowering therapies (LLT), more than half of the patients treated do not reach the lipid target indicated by the guidelines. In these patients, lipoprotein apheresis (LA) is the most effective tool to lowering apo-B containing atherogenic lipoproteins. In own center, since 1994, thanks to routinely cascade testing performed in patients who start LA, we have identified a pediatric population (30 subjects) that we analyzed retrospectively. Cascade screening, performed in subject with premature cardiovascular events or inherited dyslipidemias, is an effective approach to identified pediatric FH, a condition that pediatricians should also be aware. A dedicate network is required to investigate the involved genetic mutations and to set up a management program, including lipoprotein (a) measurement and subclinical atherosclerosis evaluation. Moreover, it is important that medical staff use a therapeutic pathway to help patients overcome discomfort associated with disease and chronic LLT, as well as improve adherence to lipid-lowering drugs. Show less

Homozygous familial hypercholesterolemia is a rare clinical phenotype with a variable expression, which is characterized by extremely elevated plasma low-density lipoprotein (LDL), tendon and skin xanthomas, and a progressive atherosclerosis. In 95% of patients, homozygous familial hypercholesterolemia is due to mutations in low-density lipoprotein receptor (LDLR) gene, which abolish (receptor-negative) or greatly reduce (receptor-defective) LDLR function. The objective of the study was the molecular and phenotypic characterization of 4 siblings with severe hypercholesterolemia. The major LDL-related genes (LDLR, APOB, PCSK9, ANGPTL3, APOE, and APOC3) were sequenced. LDLR messenger RNA, isolated from leukocytes, was reverse transcribed and sequenced. The index cases were 24-year-old identical twin sisters with long-standing tendon xanthomas and high low-density lipoprotein cholesterol (LDL-C ∼10 mmol/L) but no coronary heart disease. They were carriers of 2 LDLR mutations: (1) a previously reported mutation [p.(G335S)] inherited from the mother who had LDL-C level within normal range; (2) a novel 24 bp deletion in exon 8/intron 8 junction inherited from the hypercholesterolemic (LDL-C 6.1 mmol/L) father. The deletion allele encodes an messenger RNA with a partial deletion of exon 8, whose translation product has an in-frame deletion of 17 amino acids [p.(Glu380_Gly396del)]. Family screening revealed that the 2 siblings of the twin sisters were also compound heterozygotes but had much lower LDL-C levels (8.2 and 7.1 mmol/L). The sequence of potential modifying genes showed that the 2 siblings and the mother of the twin sisters were heterozygous for a rare missense variant of apoB [p.(S2429T)], which might have an LDL-lowering effect. We report a rare event of 4 siblings found to be compound heterozygotes for 2 LDLR gene mutations but showing a different phenotype severity. The less severely affected siblings were carriers of a rare apoB missense variant. Show less