Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis
ABSTRACT Sitosterolaemia is an extremely rare autosomal recessive disease, the key feature of which is the impairment of pathways that normally prevent absorption and retention of non-cholesterol sterols, for example plant sterols and shellfish sterols. The clinical manifestations are akin to familial hypercholesterolaemia (such as presence of tendon xanthomas and premature atherosclerosis), but with "normal to moderately elevated" cholesterol levels. The gene(s) causing sitosterolaemia was mapped to the STSL locus on human chromosome 2p21, and mutations in either of the two genes that comprise this locus, ABCG5 or ABCG8, cause this disease. Exact prevalence is unknown, but there are estimated to be 80-100 cases around the world. This rare disease has shed light into the molecular mechanisms that control sterol trafficking in the enterocyte and hepatocyte; ABCG5 and ABCG8 heterodimerise to form a sterol efflux transporter in the liver and intestine. In this review the pathophysiology, clinical manifestations and approach to clinical and laboratory diagnosis of this disease are described.
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ABSTRACT: Although homozygous familial hypercholesterolaemia (HoFH) is rare, patients with this disease have a poor prognosis, even when they receive the best available treatment, including pharmacotherapy and apheresis. The current therapeutic gap emphasizes the potential impact of new and developmental treatment options, which include lomitapide, mipomersen, anti-PCSK9 monoclonal antibodies and CETP inhibitors. It is imperative that patients with HoFH receive the most appropriate treatment as early as possible and clinical guidance is needed to provide clinicians with the information they require to expedite diagnosis and initiate effective treatment. Until now, however, guidance on the management of (HoFH) has generally been included as part of broader guidelines on dyslipidemia, FH or low-density lipoprotein (LDL)-apheresis and even in guidelines specifically on FH, HoFH has been under-represented. A consensus statement on recommendations for the management of HoFH has recently been published by a working group of the European Atherosclerosis Society. An outline of the content of the statement is presented in the current paper.Atherosclerosis Supplements 09/2014; 15(2):26–32. DOI:10.1016/j.atherosclerosissup.2014.07.004 · 9.67 Impact Factor
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ABSTRACT: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH.European Heart Journal 07/2014; 35(32). DOI:10.1093/eurheartj/ehu274 · 14.72 Impact Factor
Clinical Lipidology 12/2013; 8(6):649-658. DOI:10.2217/clp.13.60 · 0.86 Impact Factor