Hyperlipidemic myeloma, a rare form of acquired dysbetalipoproteinemia, in an HIV seropositive African female.

Dysbetalipoproteinemia (DBL) is an uncommon condition characterized by a mixed hyperlipidemia due to accumulation of remnant lipoproteins and is highly atherogenic. Typically, DBL is an autosomal recessive condition requiring an additional metabolic stress with reduced apolipoprotein E (apoE) function. However, DBL is also described in patients with multiple myeloma without the characteristic apoE2/E2 mutation seen in familial DBL. Although the underlying pathogenesis in these cases is not fully characterized, it is thought to occur due to interference with apoE function by antibodies produced from clonal plasma cells. Such cases are referred to as hyperlipidemic myeloma (HLM) and have rarely been described in the literature. To our knowledge there is no prior description of HLM in HIV positive patients in Africa. We describe a case of HLM in an African woman with underlying HIV infection who presented with phenotypic and biochemical features of DBL that responded poorly to lipid lowering therapy.

Novel PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Variants in Patients With Familial Hypercholesterolemia From Cape Town.

OBJECTIVE: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein-cholesterol and markedly increased cardiovascular risk. In patients with a genetic diagnosis, low-density lipoprotein receptor (LDLR) mutations account for >90% of cases, apolipoprotein B (APOB) mutations for ≈5% of cases, while proprotein convertase subtilisin kexin type 9 (PCSK9) gain of function mutations are rare (<1% of cases). We aimed to evaluate the functional impact of several novel PCSK9 variants in a cohort of patients with FH by genetic cascade screening and in vitro functionality assays. Approach and Results: Patients with clinically diagnosed FH underwent genetic analysis of LDLR, and if negative, sequential testing of APOB and PCSK9. We analyzed cosegregation of hypercholesterolemia with novel PCSK9 variants. Gain of function status was determined by in silico analyses and validated by in vitro functionality assays. Among 1055 persons with clinical FH, we identified nonsynonymous PCSK9 variants in 27 (2.6%) patients and 7 of these carried one of the 4 previously reported gain of function variants. In the remaining 20 patients with FH, we identified 7 novel PCSK9 variants. The G516V variant (c.1547G>T) was found in 5 index patients and cascade screening identified 15 additional carriers. Low-density lipoprotein-cholesterol levels were higher in these 15 carriers compared with the 27 noncarriers (236±73 versus 124±35 mg/dL; P<0.001). In vitro studies demonstrated the pathogenicity of the G516V variant. CONCLUSIONS: In our study, 1.14% of cases with clinical FH were clearly attributable to pathogenic variants in PCSK9. Pathogenicity is established beyond doubt for the G516V variant.

Effects of rooibos (Aspalathus linearis) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease.

ETHNOPHARMACOLOGICAL RELEVANCE: In South Africa, the plant Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is traditionally used as a "tea" referred to as rooibos or redbush. This plant has been listed as a medicinal plant based mostly on anecdotal evidence. AIMS OF THE STUDY: Despite a long history of traditional use in South Africa, very little scientific data are available from controlled clinical trials confirming its popular use. The aim of the present study was to investigate the effect of rooibos on biochemical and oxidative stress parameters in adults at risk for cardiovascular disease. MATERIALS AND METHODS: After a washout period of 2 weeks, 40 volunteers consumed six cups of fermented/traditional rooibos daily for 6 weeks, followed by a control period. Blood biochemical parameters indicative of antioxidant activity and content (total polyphenols), lipid peroxidation (conjugated dienes - CDs, thiobarbituric acid reactive substances - TBARS), redox status (total glutathione - tGSH, ratio of reduced to oxidized glutathione - GSH:GSSG), lipid profile (total cholesterol, low density lipoprotein - LDL and high density lipoprotein - HDL cholesterol and triacylglycerol levels) and liver and kidney function were measured at the end of each study period. RESULTS: Plasma antioxidant capacity was not altered, but plasma total polyphenol levels increased significantly after rooibos consumption compared with the control levels (from 79.8±16.9 mg/L to 89.8±14.1 mg/L). Significant decreases in plasma markers of lipid peroxidation were found after rooibos consumption, as reported by levels of CDs (167.3±29.5 nmol/mL vs. 108.8±20.1 nmol/mL) and TBARS (1.9±0.6 µmol/L vs. 0.9±0.3 µmol/L). Reduced glutathione (797±238 µmol/L vs. 1082±140 µmol/L) and the GSH:GSSG ratio (41±14 vs. 76±17) were both significantly increased after consumption of rooibos. The lipid profiles showed that rooibos consumption, compared with the control values, significantly decreased serum LDL-cholesterol (4.6±1.3 mmol/L vs. 3.9±0.7 mmol/L) and triacylglycerols (1.7±0.8 mmol/L vs. 1.2±0.7 mmol/L), while HDL-cholesterol (0.9±0.1 mmol/L vs. 1.2±0.2 mmol/L) was significantly increased. CONCLUSION: Confirming its popular use, consumption of fermented, traditional rooibos significantly improved the lipid profile as well as redox status, both relevant to heart disease, in adults at risk for developing cardiovascular disease.