scholarly journals Diet-Responsive Hypercholesterolemia With Cardiofaciocutaneous Syndrome Type 3

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A308-A308
Author(s):  
Nivedita Patni ◽  
Abhimanyu Garg ◽  
Chao Xing
Keyword(s):  
Total Energy ◽  
Map Kinases ◽  
De Novo ◽  
Elevated Serum ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Syndrome Type ◽  
Normal Range ◽  
Cardiofaciocutaneous Syndrome ◽  
Type 3

Abstract Background: Molecular basis of diet responsive hypercholesterolemia remains unclear. We report diet-responsive severe hypercholesterolemia in a young female with cardiofaciocutaneous syndrome type 3 (CFC3) due to a heterozygous pathogenic MAP2K1 variant, suggesting a role of common MAPK variants in LDL-cholesterol (LDL-C) response to diet. Clinical case: A 3-year-old Caucasian female with CFC3 (macrocephaly, frontal bossing, wide nasal root with depressed bridge, anteverted nares, low set fleshy ears, congenital pulmonic valve stenosis, postnatal growth deficiency, hypotonia, and neurocognitive impairment) due to a de novo heterozygous c.389A>G, p.Tyr130Cys pathogenic variant in MAP2K1, presented with extremely elevated serum total cholesterol of 446 mg/dL, triglycerides of 239 mg/dL, HDL-cholesterol of 53 mg/dL, LDL-C of 335 mg/dL (normal range < 110 mg/dL) and serum apolipoprotein B level 219 mg/dL (normal range < 90 mg/dL). Her LDL-C was 252 mg/dL a year ago and 215 mg/dL one month prior to presentation. Reducing total dietary fat to 20–25% of total energy and saturated fat to <6% of total energy over the next 4 months lowered LDL-C to 104 mg/dL. However, her weight decreased by 0.5 kg and liberalization of fat intake again increased LDL-C to 222 mg/dL. Her father has mildly elevated LDL-C of 160 mg/dL and her mother had normal LDL-C of 80 mg/dL. Her plasma phytosterol levels were normal and she had ApoE3/E3 genotype. Targeted genetic testing of the patient and parents showed a benign heterozygous LDL receptor (LDLR) variant c.2242G>A; p.Asp748Asn, (Minor allele frequency 0.00008) in the patient and her father. Whole exome sequencing of the patient and both parents showed no known disease-causing variants in LDLR, APOB, PCSK9, LDLRAP1, APOE, STAP1, LIPA, ABCG5, ABCG8 and other known hyperlipidemia-related genes. There are no previous reports of hypercholesterolemia in patients with CFC3. MAP2K1 stimulates various MAP kinases upon wide variety of extra- and intracellular signal and is involved in cell proliferation, differentiation, transcription regulation and development. Previous studies of the relationship between p42/44MAPK activation and LDLR expression in human hepatoma HepG2-derived cell line showed that that activation of the Raf-1/MEK/p42/44MAPK cascade induces LDLR expression and modulation of the Raf-1 kinase signal strength can determine LDLR expression levels. Thus, extent of MAPK activation can alter signaling of LDLR, resulting in hypercholesterolemia. Conclusion: Our case report suggests that MAP2K1 may play a significant role in LDLR signaling, and some MAP2K1 variants may be associated with diet-responsive hypercholesterolemia. Larger studies are required to assess dietary response to LDL-C in subjects with MAP2K1 variants.

The correlation between lipid metabolism disorders and the prostate cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Justyna Dłubek ◽  
Jacek Rysz ◽  
Zbigniew Jabłonowski ◽  
Anna Gluba-Brzózka ◽  
Beata Franczyk
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Cancer Progression ◽  
De Novo ◽  
Prostate Gland ◽  
Hdl Cholesterol ◽  
Atp Citrate Lyase ◽  
Male Population ◽  
Lipid Metabolism Disorders

: Prostate cancer is second most common cancer affecting male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signalling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signalling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with higher risk of more aggressive course of disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, it constitutes an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aimed to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (stearoyl-CoA desaturase) in particular, may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of the circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions, or even sub-fractions of e.g. HDL cholesterol.

Diagnosis of epilepsy using an implantable loop recorder in a child with long-QT syndrome type 3

2013 ◽  
Vol 55 (2) ◽  
pp. 251-253 ◽  
Author(s):  
Kazuhiro Takahashi ◽  
Akira Miyake ◽  
Yoshimitsu Otsuka ◽  
Masaharu Ohfu ◽  
Hitoshi Ganaha
Keyword(s):  
Long Qt Syndrome ◽  
Syndrome Type ◽  
Implantable Loop Recorder ◽  
Long Qt ◽  
Loop Recorder ◽  
Qt Syndrome ◽  
Type 3

scholarly journals Type 3 Deiodinase Role on Central Thyroid Hormone Action Affects the Leptin-Melanocortin System and Circadian Activity

Endocrinology ◽  
2016 ◽  
Vol 158 (2) ◽  
pp. 419-430 ◽  
Author(s):  
Zhaofei Wu ◽  
M. Elena Martinez ◽  
Donald L. St. Germain ◽  
Arturo Hernandez
Keyword(s):  
Energy Balance ◽  
Elevated Serum ◽  
Serum Levels ◽  
Leptin Resistance ◽  
Melanocortin System ◽  
White Adipocyte ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
The Central Nervous System ◽  
Type 3

Abstract The role of thyroid hormones (THs) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice as a result of defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3−/− brain is opposite that of the serum, exhibiting enhanced levels of TH action. Because the brain, particularly the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3−/− mice and determine whether it is associated with hypothalamic abnormalities. Here we show that Dio3−/− mice of both sexes exhibit decreased adiposity, reduced brown and white adipocyte size, and enhanced fat loss in response to triiodothyronine (T3) treatment. They also exhibit increased TH action in the hypothalamus, with abnormal expression and T3 sensitivity of genes integral to the leptin-melanocortin system, including Agrp, Npy, Pomc, and Mc4r. The normal to elevated serum levels of leptin, and elevated and repressed expression of Agrp and Pomc, respectively, suggest a profile of leptin resistance. Interestingly, Dio3−/− mice also display elevated locomotor activity and increased energy expenditure. This occurs in association with expanded nighttime activity periods, suggesting a disrupted circadian rhythm. We conclude that DIO3-mediated regulation of TH action in the central nervous system influences multiple critical determinants of energy balance. Those influences may partially compensate each other, with the result likely contributing to the decreased adiposity observed in Dio3−/− mice.

scholarly journals Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment

2008 ◽  
Vol 54 (6) ◽  
pp. 1038-1045 ◽  
Author(s):  
Gilles Lambert ◽  
Nicolas Ancellin ◽  
Francesca Charlton ◽  
Daniel Comas ◽  
Julia Pilot ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Polyclonal Antibodies ◽  
Sandwich Elisa ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Diabetic Patients ◽  
Plasma Triglycerides ◽  
Fenofibrate Treatment ◽  
Before And After ◽  
Fenofibrate Intervention

Abstract Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment. Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment. Results: We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048). Conclusions: We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol–lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.

Silvery hair with dyschromatosis: Griscelli syndrome type 3 or familial gigantic melanocytosis

2018 ◽  
Vol 45 (12) ◽  
pp. 918-922
Author(s):  
Meenakshi Batrani ◽  
Akhilesh Thole ◽  
Asha Kubba ◽  
Khushbu Mahajan
Keyword(s):  
Syndrome Type ◽  
Griscelli Syndrome ◽  
Type 3

HDL cholesterol and LDL receptor activity

1983 ◽  
Vol 49 (2) ◽  
pp. 215-217 ◽  
Author(s):  
C. Cortese ◽  
N.E. Miller ◽  
C.B. Marenah ◽  
B. Lewis
Keyword(s):  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Receptor Activity

scholarly journals Reference intervals for serum lipids and prevalence of dyslipidaemia in 6–12-year-old children: The Health Oriented Pedagogical Project (HOPP)

2018 ◽  
Vol 46 (21_suppl) ◽  
pp. 21-27 ◽  
Author(s):  
Martin Frank Strand ◽  
Per Morten Fredriksen ◽  
Ole Petter Hjelle ◽  
Morten Lindberg
Keyword(s):  
Total Cholesterol ◽  
Serum Lipids ◽  
Venous Blood ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Reference Intervals ◽  
Age And Gender ◽  
Norwegian Population ◽  
And Gender

Aims: Elevated serum lipid concentrations in childhood are thought to be risk factors for the development of cardiovascular disease later in life. The present study aims to provide age- and gender-related reference intervals for total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol in healthy school children. We also investigated the prevalence of dyslipidaemia using the published criteria for these biomarkers. Methods: Venous blood and anthropometric data were collected from 1340 children in the HOPP study, aged between 6 and 12 years. Age- and gender-related reference intervals (2.5th and 97.5th percentiles) were established according to the IFCC recommendations, using the software RefVal 4.10. Results: Gender differences were observed for total cholesterol and non-HDL cholesterol, but not for HDL cholesterol. Age differences were observed for total cholesterol. The reference intervals were in the range of 3.1–5.9 mmol/L for total cholesterol, 1.0–2.4 mmol/L for HDL cholesterol and 1.4–4.2 mmol/L for non-HDL cholesterol. Dyslipidaemia prevalence was as follows: increased TC 9.6%, decreased HDL 1.6%, and increased non-HDL 5.6%. Conclusions: Age- and gender-related reference intervals in a Norwegian population are similar to those reported in other countries. The prevalence of dyslipidaemia among Norwegian children is significant, emphasising the importance of appropriate reference intervals in clinical practice.

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