Cases Of Heterozygous Familial Hypercholesterolemia Research Articles

Abstract #1093061: A Case of Heterozygous Familial Hypercholesterolemia in a Patient With a History of Statin-Induced Myopathy With Incomplete Response to PCSK9 Inhibitor Monotherapy

A patient with markedly elevated LDL and a history of statin-induced myopathy was referred to Lipid Clinic for management of hyperlipidemia. Genetic testing was performed which confirmed the diagnosis of Familial Hypercholesterolemia. It also revealed the presence of a mutation of SLCO1B1 which has been associated with statin-induced myopathy. The patient did not reach the desired LDL goal with PCSK9 inhibitor alone. This case report explores the management decisions made to balance the benefits of LDL reduction with the risk of statin-induced myopathy in a patient with multiple mutations contributing to his hyperlipidemia.

Familial Hypercholesterolemia with Tendinous Xanthomas and Achilles Tendinitis – A Forgotten Dermato-Rheumatologic Association

Abstract Familial hypercholesterolemia (FH) is a disorder of lipoprotein metabolism with dermatological and rhematological manifestations. Tendinous xanthomata (TX) are a hallmark of this disease. They are associated with recurrent tendinitis and tendon damage, an aspect of the clinical presentation, which is not well-known among dermatologists. We report two cases of heterozygous familial hypercholesterolemia, where the patients started developing tendinous xanthomata early in their life, with progressive increase in the number and size of lesions. However, they presented late, only when the recurrent attacks of tendinitis became severe. We present these cases to highlight the rheumatologic features, which may be the first symptom of heterozygous familial hypercholesterolemia.

Heterozygous familial hypercholesterolemia case study

To examine a case of heterozygous familial hypercholesterolemia (HeFH) in a primary care setting and to review the epidemiology, pathophysiology, etiology, and treatment guidelines to reduce the mortality related to this disease process. Findings from the history, physical exam, and laboratory results of a young French Canadian male presenting to a primary care office. Evidence-based literature search included Ovid MEDLINE, PubMed, National Lipid Association, and e-medicine website. Familial hypercholesterolemia is a serious and common genetic disorder that results in premature atherosclerosis. Early screening, detection, and treatment are vital in order to reduce the associated morbidity and mortality. Clinicians need to understand hypercholesterolemia and the atherogenic process. Physical exam and laboratory findings are key to the early identification and intervention for children and adults at risk for early cardiovascular disease.

The first recorded heterozygote for familial hypercholesterolemia

In a recent review, Ose cites the Madonna Lisa Maria de Gherardini (1479–1506), the subject of Leonardo da Vinci’s painting, Mona Lisa, as the first recorded case of heterozygous familial hypercholesterolemia (HeFH). This opinion is based on what appears to be a xanthelasma in the inner canthus of her left orbit and a swelling just behind the metacarpophalangeal joint of her left hand. The swelling is not definitely a tendon xanthoma, although a gouty tophus, which it might also resemble, would be unlikely in a women of her age unless she had chronic renal disease. The xanthelasma looks more convincing, but could be an epidermal cyst. Indisputable xanthelasmata did not appear in any medical text until Rayer’s Atlas of Skin Disorders (1835). His illustration is labelled ‘‘Plaques jaunes disposes d’une maniere, symmetrique sur les paupieres des deux yeux.’’ Addison and Gull were next to describe xanthelasmata, which they termed ‘‘vitiligoidea plana’’ in 1851. At lease three of their cases had the dyslipidemia of chronic obstructive jaundice and another had what we would currently regard as dysbetalipoproteinemia. Tendon xanthomata, the characteristic feature of HeFH, were believed to have first been recorded by Frans Hals in his ‘‘Portrait of an Elderly Lady’’ painted in 1633. The dorsa of her hands undoubtedly show tendon xanthomata. The fact that she reached old age is quite compatible with the evidence that HeFH was not associated with early cardiovascular death in The Netherlands until around the turn of the 19th century. The first medical descriptions of tendon xanthomata as a feature of HeFH were made in the 20th

Flow cytometry with a monoclonal antibody to the low density lipoprotein receptor compared with gene mutation detection in diagnosis of heterozygous familial hypercholesterolemia

We used a fluorescence flow cytometry assay with a monoclonal low density lipoprotein (LDL) receptor-specific antibody to detect LDL receptor expression on blood T lymphocytes and monocytes. We prepared peripheral blood mononuclear cells from patients with genetically verified LDL receptor-defective (Trp66-Gly mutation, n = 17) or receptor-negative (Trp23-stop mutation, n = 17) heterozygous familial hypercholesterolemia (FH) and from healthy individuals (n = 24). The cells were stimulated to express the maximum amount of LDL receptor by preincubation in lipoprotein-deficient medium. A dual-labeling technique allowed flow cytometric analysis of LDL receptor expression on cells identified by fluorescently conjugated surface marker antibodies. Knowing the LDL receptor gene mutation of the FH patients allowed us to compare the diagnostic capability of this functional assay with the DNA diagnosis and to validate the assay with molecular genetics instead of clinical indices of heterozygous FH. T lymphocytes expressed more LDL receptors and gave better diagnostic results than monocytes, and cells from patients with either the Trp66-Gly or the Trp23-stop mutation had variable but significantly reduced LDL receptor expression. The data indicate that this fluorescence flow cytometry assay is unsuitable for diagnosis of individual cases of heterozygous FH but that it may be useful for functionally characterizing mutations in the LDL receptor gene.

高脂血症患者に対するProbucolおよびPantethine併用の効果

It is well known that Probucol induce marked reduction of serum cholesterol (TC) and LDL-cholesterol (LDL-C) levels. However, a problem exisits that HDL-C also decrease significantly in the Probucol administration. It might be well effective, if reduction of HDL-C by Probucol could be prevented by the utilisation with other drugs together. From the above mentioned points of view, effects of administration of Probucol and Pantethine together on the serum lipids, lipoproteins and apolipoproteins were investigated in this study, since Pantethine is known to activate lipolitic activity and stimulate biosynthesis of HDL apo A-I.Methods:Ten cases of heterozygous familial hypercholesterolemia and combined hyperlipemia were subdivided into two groups. Then, 750mg/day of Probucol and 600mg/day of Pantethine were given for 8 weeks into first group, and 1, 500mg/day of Probucol and 600mg/day of Pantethine to second group. Lipoprotein fractions were ultracentrifugally separated and TC, PL were measured by emzymatic method and tryglyceride (TG) was measured by acetylacetone method. LCAT was measured by Akanuma-Nagasaki method.Results:1) By the administration of Probucol 750mg/day and Pantethine 600mg/day (1st group), serum TC, serum TG, LDL-C, VLDL-TG significantly decreased (13%, 12%, 18%, 18%, respectively). However, HDL-C remained nochange. In HDL subfraction, HDL2 showed slight increasing tendency and the ratio of HDL2 and HDL3 was elevated from 0.50±0.15 to 0.62±0.08. HDL apo A-I also increased from 56.7±0.7% to 61.2±4.2%. LCAT was not significantly changed.2) By administration of Probucol 1, 500mg/day and Pantethine 600mg/day (2nd group), serum TC, LDL-C markedly decreased. (34%, 32 respectively) and extends of decrease of various lipids in 2nd group were more than those in 1st group. In this group, HDL-C decreased markedly. Serum TG and VLDL-TG decreased slightly. In HDL subfraction, HDL2 and HDL3 were markedly decreased (46%, 30% respectively) and the ratio of HDL2 and HDL3 was also decreased by 20%. HDL apo A-I and LCAT were decreased slightly.Conclusion:Synergistic administration of Probucol and Pantethine is effective to prevent the HDL-C reduction by Probucol when dose of Probucol is maintained under 750mg/day.

A case of heterozygous familial hypercholesterolemia associated with hyperthyroidism: Effects of triiodothyronine on low-density lipoprotein receptor and cholesterol synthesis

A 58-year-old patient with heterozygous familial hypercholesterolemia (FH) showed normal levels of serum cholesterol (193 mg/dL) in coexistence with hyperthryoidism. After hyperthyroidism therapy with radioiodine and methimazole, the patient's lipid profile showed high concentrations of cholesterol (whole serum 318 mg/dL, VLDL 35 mg/dL, LDL 217 mg/dL, HDL 44 mg/dL). There was a significant inverse correlation between serum cholesterol levels and serum thyroxine levels ( r = −0.815, p < 0.01). Effects of triiodothyronine on LDL degradation and cholesterol synthesis from 14C-labeled acetate were studied in cultured skin fibroblasts. Triiodothyronine (T 3) stimulated both LDL degradation and cholesterol synthesis in the cells from normal subjects and patients with heterozygous FH. The T 3 increased cellular cholesterol synthesis markedly in the cells from patients with homozygous FH but did not increase LDL receptor activity. These results suggest that normal serum cholesterol levels in our case result in part from an enhancement of LDL receptors by thyroid hormone.