DOCSLIB.ORG

Familial Hypobetalipoproteinemia (FHBL) Is a Disorder That Impairs the Body's Ability to Absorb and Transport Fats, Causing Low Levels of Cholesterol in the Blood

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Familial Hypobetalipoproteinemia (FHBL) Is a Disorder That Impairs the Body's Ability to Absorb and Transport Fats, Causing Low Levels of Cholesterol in the Blood Prepared by : Eman Elkomy Supervised by : Ass.Prof. Dr./ Ragaa Abdelkadr Conditions with abnormally low levels of LIPOPROTEINS in the blood. This may involve any of the lipoprotein subclasses, including ALPHA- LIPOPROTEINS (high-density lipoproteins); BETA- LIPOPROTEINS (low-density lipoproteins); and PREBETA-LIPOPROTEINS (very-low-density lipoproteins). The unexpected finding of low cholesterol or low LDL cholesterol in a patient not taking a lipid-lowering drug should prompt a diagnostic evaluation, including measurements of AST (aspartate aminotransferase), ALT (alanine aminotransferase), and thyroid-stimulating hormone; a negative evaluation suggests a possible primary cause. Examples of primary disorders in which single or multiple genetic mutations result in underproduction or increased clearance of LDL. Abetalipoproteinemia Hypobetalipoproteinemia Chylomicron retention disease Loss of function mutations of PCSK9 (proprotein convertase subtilisin-like/kexin type 9) are another cause of low LDL levels. There are no adverse consequences and no treatment, Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats, causing low levels of cholesterol in the blood. The severity of the condition varies widely. Mildly affected people may have no signs or symptoms. Many affected people develop an abnormal buildup of fats in the liver (called hepatic steatosis, or fatty liver). In severe cases, this may progress to cirrhosis. Some people also have digestive problems in childhood, resulting in failure to thrive. FHBL is usually caused by mutations in the APOB gene. In a few cases, it may be caused by mutations in other genes, or the cause may be unknown. It is inherited in an autosomal codominant manner. Management may include reducing fat in the diet and vitamin E supplementation. A new case of a Japanese patient with familial hypobetalipoproteinemia (FHBL) caused by a protein-truncating variant in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (c.1090_1091del/p.Pro364ArgfsTer62) was identified and among her family. None of them exhibited atherosclerotic cardiovascular diseases nor any other complications associated with low LDL cholesterol, including fatty liver, neurocognitive disorders, or cerebral hemorrhaging. . In racent study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants-c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)-in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL. In another racent study,Four novel variants of APOB gene identified in seven FHBL-1 heterozygotes. (c.237+1G>A, c.818+5G>A, c.3000-1G>T, and c.3842+1G>A), predicted in silico to obliterate splice site activity, were found to generate abnormal transcripts. Chylomicron retention disease is an inherited disorder that impairs the normal absorption of fats, cholesterol, and certain vitamins from food. The features of chylomicron retention disease primarily affect the gastrointestinal system and nervous system. Chylomicron retention disease begins in infancy or early childhood. Affected children have slow growth and weight gain, frequent (chronic) diarrhea, and foul-smelling stools (steatorrhea). They also have reduced blood cholesterol levels (hypocholesterolemia). Some individuals with chylomicron retention disease develop an abnormal buildup of fats in the liver called hepatic stenosis and can have an enlarged liver. other features of chylomicron retention disease develop later in childhood and often impair the function of the nervous system. affected people may develop decreased reflexes (hyporeflexia) and a decreased ability to sense vibrations. rarely, affected individuals have heart abnormalities or muscle wasting (amyotrophy). Mutations in a gene called SAR1B cause chylomicron retention disease. The SAR1B gene provides instructions for making a protein that is needed for the transport of molecules called chylomicrons. During digestion, chylomicrons are formed within cells called enterocytes that line the small intestine and absorb nutrients. Chylomicrons are needed to absorb fat-soluble vitamins and carry fats and cholesterol from the small intestine into the bloodstream. SAR1B gene mutations cause the retention of chylomicrons within enterocytes and prevent their release into the bloodstream. Impaired chylomicron transport causes severely decreased absorption (malabsorption) of dietary fats and fat-soluble vitamins, leading to nutritional and developmental problems in people with chylomicron retention disease. Affected individuals are unable to absorb sufficient fats, cholesterol, and vitamins that are necessary for normal growth and development. chylomicron retention disease is a rare condition with approximately 50 cases described worldwide. this condition is inherited in an autosomal recessive pattern Racent study reported 4 children with intestinal lipid malabsorption were found to have chylomicron retention disease due to 3 novel variants in the SAR1B gene.Case 1, a 9-month-old male, was found to be homozygous for a SAR1B variant (c.49 C>T), predicted to encode a truncated Sar1b protein devoid of function (p.Gln17*). Case 2, a 4-year-old male, was found to be homozygous for a SAR1B missense variant [c.409 G>C, p.(Asp137His)], which affects a highly conserved residue close to the Sar1b guanosine recognition site. Case 3, a 6-year-old male, was found to be homozygous for an ∼6 kb deletion of the SAR1B gene, which eliminates exon 2; this deletion causes the loss of the ATG translation initiation codon in the SAR1B mRNA. The same homozygous mutation was found in an 11-month-old child (case 4) who was related to case 3. is a very rare condition that affects fat and vitamin absorption by the intestines and liver, leading to very low LDL-cholesterol and malnutrition. Early symptoms of this condition include diarrhea, vomiting, and poor growth. Without treatment, later complications may include muscle weakness, poor night and color vision, tremors, and speech difficulties. The long-term outcome can be difficult to predict. Abetalipoproteinemia is diagnosed based on clinical exam, laboratory tests showing abnormally low cholesterol, and confirmed by genetic testing. This condition is caused by genetic variants in the MTTP gene and is inherited in an autosomal recessive pattern. the signs and symptoms of abetalipoproteinemia usually appear in the first few months of life.They can include: inability to absorb fats and some vitamins poor growth in infancy digestive symptoms such as diarrhea and steatorrhea (foul- smelling stools) abnormal, star-shaped red blood cells (acanthocytosis) Because abetalipoproteinemia is extremely rare, the course of the disease is difficult to predict. This condition is usually diagnosed in infancy due to diarrhea, vomiting and poor growth. Most individuals with this condition are treated with excess vitamins and a special, fat-controlled diet and have few complications. Untreated individuals with abetalipoproteinemia can develop gradual vision loss, muscle weakness, tremors, and slow or slurred speech that gets worse over time. This condition has been treated with a low fat diet and vitamin supplements. Most people with abetalipoproteinemia who are treated do not develop complications. Abetalipoproteinemia is very rare and the exact prevalence is difficult to predict. Approximately 100 cases have been reported in the literature.[ Differential diagnoses include metabolic diseases with hepatic overload, with steatosis and/or hepatomegaly, atypical diseases of the central and peripheral nervous system, and secondary causes of hypocholesterolemia (iatrogenic or systemic). Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Racently,LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband's plasma, but with undetectable enzyme activity compared to control relatives. Familial LCAT deficiency (FLD) patients accumulate lipoprotein-X (LP-X), an abnormal nephrotoxic lipoprotein enriched
Load more

Recommended publications
  • Genes in Eyecare Geneseyedoc 3 W.M
    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
    [Show full text]
  • Lipid Deposition at the Limbus
    Eye (1989) 3, 240-250 Lipid Deposition at the Limbus S. M. CRISPIN Bristol Summary Lipid deposition at the limbus is a feature of familial and non-familial dyslipopro­ teinemias and can also occur without apparent accompanying systemic abnormality. Hyperlipoproteinemia, most notably type II hyperlipoproteinemia, is frequently associated with bilateral corneal arcus, with less common association in types III, IV and V. Diffuse bilateral opacification of the cornea with accentuation towards the limbus is a feature of HDL deficiency syndromes and LCAT deficiency. Whereas the lipid accumulation of hyperlipoproteinemia may be representative of excessive insudation of lipoprotein from plasma into the cornea that of hypoliproteinemia is more likely to be a consequence of defective lipid clearance. The situation is yet further complicated by the modifying influences of secondary factors. both local and systemic. Lipid may be deposited at the limbus in a so. Both local and systemic factors can influ­ variety of situations; most commonly it ence lipid deposition in this region and their accumulates as a consequence of excessive inter-relationships are complex and often lipid entry or defective lipid clearance over a poorly understood. Some of the local factors long period of time, but this is not invariably which have been investigated include normal and abnormal structure and function; the effects of temperature and vasculature; and the modifying influences of certain ocular disorders. LIVER Local lipoprotein metabolism of cornea and limbus has received little study but there is a wealth of information available concerning systemic plasma lipoproteins in health and disease and a number of dyslipoproteinemias VLDLI LDL have been reported in which corneal lipid deposition is one of the clinical features.
    [Show full text]
  • Commonly Used Lipidcentric ICD-10 (ICD-9) Codes
    Commonly Used Lipidcentric ICD-10 (ICD-9) Codes *This is not an all inclusive list of ICD-10 codes R.LaForge 11/2015 E78.0 (272.0) Pure hypercholesterolemia E78.3 (272.3) Hyperchylomicronemia (Group A) (Group D) Familial hypercholesterolemia Grütz syndrome Fredrickson Type IIa Chylomicronemia (fasting) (with hyperlipoproteinemia hyperprebetalipoproteinemia) Hyperbetalipoproteinemia Fredrickson type I or V Hyperlipidemia, Group A hyperlipoproteinemia Low-density-lipoid-type [LDL] Lipemia hyperlipoproteinemia Mixed hyperglyceridemia E78.4 (272.4) Other hyperlipidemia E78.1 (272.1) Pure hyperglyceridemia Type 1 Diabetes Mellitus (DM) with (Group B) hyperlipidemia Elevated fasting triglycerides Type 1 DM w diabetic hyperlipidemia Endogenous hyperglyceridemia Familial hyperalphalipoproteinemia Fredrickson Type IV Hyperalphalipoproteinemia, familial hyperlipoproteinemia Hyperlipidemia due to type 1 DM Hyperlipidemia, Group B Hyperprebetalipoproteinemia Hypertriglyceridemia, essential E78.5 (272.5) Hyperlipidemia, unspecified Very-low-density-lipoid-type [VLDL] Complex dyslipidemia hyperlipoproteinemia Elevated fasting lipid profile Elevated lipid profile fasting Hyperlipidemia E78.2 (272.2) Mixed hyperlipidemia (Group C) Hyperlipidemia (high blood fats) Broad- or floating-betalipoproteinemia Hyperlipidemia due to steroid Combined hyperlipidemia NOS Hyperlipidemia due to type 2 diabetes Elevated cholesterol with elevated mellitus triglycerides NEC Fredrickson Type IIb or III hyperlipoproteinemia with E78.6 (272.6)
    [Show full text]
  • Evaluation and Treatment of Hypertriglyceridemia: an Endocrine Society Clinical Practice Guideline
    SPECIAL FEATURE Clinical Practice Guideline Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline Lars Berglund, John D. Brunzell, Anne C. Goldberg, Ira J. Goldberg, Frank Sacks, Mohammad Hassan Murad, and Anton F. H. Stalenhoef University of California, Davis (L.B.), Sacramento, California 95817; University of Washington (J.D.B.), Seattle, Washington 98195; Washington University School of Medicine (A.C.G.), St. Louis, Missouri 63110; Columbia University (I.J.G.), New York, New York 10027; Harvard School of Public Health (F.S.), Boston, Massachusetts 02115; Mayo Clinic (M.H.M.), Rochester, Minnesota 55905; and Radboud University Nijmegen Medical Centre (A.F.H.S.), 6525 GA Nijmegen, The Netherlands Objective: The aim was to develop clinical practice guidelines on hypertriglyceridemia. Participants: The Task Force included a chair selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence, e-mail discussion, conference calls, and one in-person meeting. The guidelines were reviewed and approved sequen- tially by The Endocrine Society’s CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: The Task Force recommends that the diagnosis of hypertriglyceridemia be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150–999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hyper- triglyceridemia (triglycerides of Ͼ 1000 mg/dl) be considered a risk for pancreatitis.
    [Show full text]
  • Difference Between Dyslipidemia and Hyperlipidemia Key Difference – Dyslipidemia Vs Hyperlipidemia
    Difference Between Dyslipidemia and Hyperlipidemia www.differenebetween.com Key Difference – Dyslipidemia vs Hyperlipidemia Dyslipidemia and hyperlipidemia are two medical conditions that affect the lipid levels of the body. Any deviation of the lipid level of the body from the normal and clinically appropriate values is identified as dyslipidemia. Hyperlipidemia is a form of dyslipidemia where the lipid levels are abnormally elevated. The key difference between dyslipidemia and hyperlipidemia is that dyslipidemia refers to any abnormality in the lipid levels whereas hyperlipidemia refers to an abnormal elevation in the lipid level. What is Dyslipidemia? Any abnormality in the lipid levels of the body is identified as dyslipidemia. Different forms of dyslipidemia include Hyperlipidemia Hypolipidemia Lipid levels of the body are abnormally reduced in this condition. Severe protein energy malnutrition, severe malabsorption, and intestinal lymphangiectasia are the causes. Hypolipoproteinemia This disease is caused by genetic or acquired causes. The familial form of hypolipoproteinemia is asymptomatic and does not require treatments. But there are some other forms of this condition which are extremely severe. Genetic disorders associated with this condition are, Abeta lipoproteinemia Familial hypobetalipoproteinemia Chylomicron retention disease Lipodystrophy Lipomatosis Dyslipidemia in pregnancy What is Hyperlipidemia? Hyperlipidemia is a form of dyslipidemia that is characterized by abnormally elevated lipid levels. Primary Hyperlipidemia Primary hyperlipidemias are due to a primary defect in the lipid metabolism. Classification Disorders of VLDL and chylomicrons- hypertriglyceridemia alone The commonest cause of these disorders is the genetic defects in multiple genes. There is a modest increase in the VLDL level. Disorders of LDL- hypercholesterolemia alone There are several subgroups of this category Heterozygous Familial Hypercholesterolemia This is a fairly common autosomal dominant monogenic disorder.
    [Show full text]
  • A Neonatal Hypertriglyceridemia Presenting with Respiratory Distress: a Rare Case Report
    International Journal of Contemporary Pediatrics Bhatia S et al. Int J Contemp Pediatr. 2018 Nov;5(6):2347-2349 http://www.ijpediatrics.com pISSN 2349-3283 | eISSN 2349-3291 DOI: http://dx.doi.org/10.18203 /2349-3291.ijcp20183839 Case Report A neonatal hypertriglyceridemia presenting with respiratory distress: a rare case report Sumit Bhatia*, Payas Joshi, Jay Kishore, Chetnanand Jha Department of Neonatology, Max Superspeciality, Patparganj, New Delhi, India Received: 16 August 2018 Accepted: 25 August 2018 *Correspondence: Dr. Sumit Bhatia, E-mail: sumitbhatia0188yahoo.com Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Neonatal hypertriglyceridemia is a very rare condition. Diagnosis in neonatal period is very difficult and is usually diagnosed when acute pancreatitis sets in. Early diagnosis is important as it can prevent the complications associated with the condition that is acute pancreatitis and pancreatic necrosis. Here we present a case of neonatal hypertriglyceridemia who presented to us with respiratory distress but was diagnosed early due to the presence of highly viscous and milky blood. This holds importance as early treatment can reduce the complications and morbidity associated with familial hypertriglyceridemia. Keywords: Hypertriglyceridemia, Milky blood, Neonatal INTRODUCTION lipoproteins, an increased level of cholesterol with an elevated level of Tg, and relative frequency slightly Familial hypertriglyceridemia (FH) is a very rare higher, about 5%.4 Lipid disorders can occur as a primary condition occurring in around 1 % of population.1 Plasma event or secondary to the underlying disease.
    [Show full text]
  • Regulation of Vitamin E and the Tocopherol Transfer
    REGULATION OF VITAMIN E AND THE TOCOPHEROL TRANSFER PROTEIN By LYNN M. ULATOWSKI Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Dissertation Advisor: Dr. Danny Manor Department of Nutrition CASE WESTERN RESERVE UNIVERSITY May 2012 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of ________________________Lynn M. Ulatowski_______________ candidate for the ___________Doctor of Philosophy____degree *. (signed) _____Colleen Croniger____________________________ (chair of the committee) _____Danny Manor________________________________ _____Thomas Kelley_______________________________ _____Ruth Siegel__________________________________ _____Laura Nagy__________________________________ ________________________________________________ (date ) March 12, 2012 *We also certify that written approval has been obtained for any proprietary material contained therein. i Dedication I dedicate this thesis to my wonderful daughter Lindsey and my mother Joyce. I know my mom’s example shaped my ability to raise such an extraordinary daughter. Lindsey, you are my inspiration and I love you to infinity. I share the success of earning a PhD with my family and Jeff, for I am convinced without their support and love it would not have been possible. ii Table of Contents Table of Contents .............................................................................................. iii List of Tables ....................................................................................................
    [Show full text]
  • Hypocholesterolemia in Clinically Serious Conditions – Review
    Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008, 152(2):181–189. 181 © P. Vyroubal, C. Chiarla, I. Giovannini, R. Hyspler, A. Ticha, D. Hrnciarikova, Z. Zadak HYPOCHOLESTEROLEMIA IN CLINICALLY SERIOUS CONDITIONS – REVIEW Pavel Vyroubala*, Carlo Chiarlab, Ivo Giovanninib, Radek Hysplera, Alena Tichaa, Dana Hrnciarikovaa, Zdenek Zadaka a Department of Gerontology and Metabolism, Faculty Hospital and Faculty of Medicine in Hradec Kralove, Sokolska 581, Hradec Kralove, Czech Republic b Centro de Studio per la fi ssiopatologia, Université Cattolica del S.Cuore, L.go A.Gemelli 8-00168 Roma, Italy e-mail: [email protected] Received: October 21, 2008; Accepted (with revisions): August 5, 2008 Key words: Cholesterol/Hypocholesterolemia/Hypolipoproteinemia/SIRS/Cytokines/Polytrauma/ Sepsis/Critically ill Background: Cholesterol is an essential component of cell membranes, precursor of steroids, biliary acids and other components of serious importance in live organism. Cholesterol synthesis is a complicated and energy-demand- ing process. Real daily need of cholesterol and mechanisms of decline cholesterol levels in critical ill are unknown. During stressful situations a signifi cant hypocholesterolaemia may be found. Hypocholesterolemia has been known for a number of years to be a signifi cant prognostic indicator of increased morbidity and mortality connected with a whole spectrum of pathological conditions. The aim of article is the elucidation of the role and importance of hypo- cholesterolaemia during the intensive care. Methods and Results: We examined studies that are engaged in problems of hypocholesterolemia in critically ill. Very low levels of total as well as LDL cholesterol are most frequently found in serious polytrauma, after extensive surgery, in serious infections, in protracted hypovolemic shock.
    [Show full text]
  • Grubb Dissertation New 1-2-13
    CHARACTERIZATION OF FACTORS THAT IMPACT APOLIPOPROTEIN B SECRETION AND ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION by Sarah Renee Grubb B.S., Mercyhurst College, 2007 Submitted to the Graduate Faculty of the Kenneth P. Dietrich School of Arts and Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2013 UNIVERSITY OF PITTSBURGH Dietrich School of Arts and Sciences This dissertation was presented by Sarah Renee Grubb It was defended on November 9, 2012 and approved by Deborah L. Chapman, Ph.D., Associate Professor Joseph Martens, Ph.D., Assistant Professor James M. Pipas, Ph.D., Professor Jonathan Minden, Ph.D., Professor Dissertation Advisor: Jeffrey L. Brodsky, Ph.D., Professor ii Copyright © by Grubb 2013 iii CHARACTERIZATION OF FACTORS THAT CONTRIBUTE TO APOLIPOPROTEIN B SECRETION AND DEGRADATION Sarah Renee Grubb, PhD University of Pittsburgh, 2013 Apolipoprotein B (ApoB) is a lipoprotein that transports cholesterol and triglycerides through the bloodstream. High plasma levels of ApoB are one of the strongest risk factors for the development of Coronary Artery Disease. Using a yeast expression system for ApoB, I focused my research on identifying new therapeutic targets to reduce the amount of ApoB secreted into the bloodstream. One way that ApoB levels are regulated is through Endoplasmic Reticulum- Associated Degradation (ERAD), a quality control mechanism that rids the secretory pathway of misfolded proteins. Due to ApoB’s hydrophobic character and high number of disulfide bonds, one class of proteins that I hypothesized may contribute to ApoB ERAD was the Protein Disulfide Isomerase (PDI) family. PDI’s catalyze the oxidation, reduction, and isomerization of disulfide bonds and some also have chaperone-like activity.
    [Show full text]
  • Xanthoma of Bone
    urgica f S l O o s n c Alhaneedi et al., Arch Surg Oncol 2018, 4:1 e o v i l o h g DOI: 10.4172/2471-2671.1000130 c y r A Archives of Surgical Oncology ISSN: 2471-2671 Review Article Open Access Xanthoma of Bone: A Mini Review Ghalib Alhaneedi1*, Motasem Salameh1 and Hasan AbuHejleh2 1Department of Orthopedic Surgery, Hamad Medical Corporation, Alrayan Street, Doha, Qatar 2Department of Orthopedic Surgery, Hamad General Hospital, Alrayan Street, Doha, Qatar *Corresponding author: Ghalib Alhaneedi, Department of Orthopedic Surgery, Senior Consultant Orthopedic Surgeon, Hamad Medical Corporation, Alrayan Street, Doha, Qatar, Tel: 0097455975125; E-mail: [email protected] Received date: Nov 09, 2017; Accepted date: Jan 2, 2018; Published date: Jan 9, 2018 Copyright: © 2017 Alhaneedi G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Xanthoma of bone is a rare benign primary bone disorder with a hallmark of cholesterol deposition in the bone frequently seen in men and in patients over 20 years of age. This mini review provides an overview of the known clinical, radiological and pathological features of the disease which can mimic primary bone tumors or metastatic lesions. In this review, we focus on the current considerations in the use of clinical and radiological features, lipid profile and histopathological study for the definitive diagnosis. Despite this wealth of features, the definitive diagnosis of bone xanthoma continues to be difficult.
    [Show full text]
  • As Lipoproteins Lipoproteins and Related Clinical Problems
    Lipoprotein Metabolism By Reem M. Sallam, M.D., MSc., Ph.D. Introduction Lipid compounds: Relatively water insoluble Therefore, they are transported in plasma (aqueous) as Lipoproteins Lipoproteins and Related Clinical Problems • Atherosclerosis and hypertension • Coronary heart diseases • Lipoproteinemias (hypo- and hyper-) • Fatty liver Lipoprotein Structure Protein part: Apoproteins or apolipoproteins Abbreviations: Apo-A, B, C, D, E Functions: Structural and transport function Enzymatic function Ligands for receptors Lipid part: • According to the type of lipoproteins • Different lipid components in various combinations Spherical molecules of lipids and proteins (apoproteins) Outer coat: - Apoproteins - Phospholipids - Cholesterol (Unesterified) Inner core: - TG - Cholesterol ester (CE) Lipoprotein Structure Types of Lipoproteins • What’s different in various types of lipoproteins? They differ in lipid and protein composition and therefore, they differ in - Size and density - Electrophoretic mobility Chylomicrons Very low density Types and Lipoprotein (VLDL) Composition Low density of Lipoprotein (LDL) Lipoproteins High density Lipoprotein (HDL) Ultracentrifugation of Lipoproteins Lipoprotein Electrophoresis Plasma Lipoproteins For triacylglycerol transport (TG-rich): - Chylomicrons: TG of dietary origin - VLDL: TG of endogenous (hepatic) synthesis For cholesterol transport (cholesterol-rich): LDL: Mainly free cholesterol HDL: Mainly esterified cholesterol Chylomicrons • Assembled in intestinal mucosal cells • Lowest density • Largest
    [Show full text]
  • 10,11-Antihyperlipidemia Drugs
    Drugs for Hyperlipidemia Titles Very important Extra information Doctor’s notes Hyperlipidemia: it is an abnormal increase in blood lipids and/or Lipoproteins are classified into five major families which differ in Lipoproteins that includes: the amount of cholesterol, triglycerides and types of Apo-proteins • Cholesterol (C). they contain: • Triglycerides (TG). o Chylomicrons (CM). • Phospholipids (PL). o Very low density lipoprotein (VLDL). • Cholesterol esters (CE). o Intermediate - density lipoproteins (IDL) • Non-esterified fatty acids (NEFA). o Low density lipoprotein (LDL). o High density lipoprotein (HDL). v Hyperlipidemia is a major cause of atherosclerosis which may lead to coronary artery diseases and ischemic cerebrovascular diseases. Ø Lipids originate from two sources: • Endogenous lipids: synthesized in the liver. • Exogenous lipids: ingested and processed in the intestine. Lipoprotein: • Endogenous molecules that contain both proteins and lipids in their Atherogenic particles: structures. • Low density lipoprotein (LDL). • They transport lipid around the body in the blood. • Very low density lipoprotein (VLDL). • Intermediate - density lipoproteins (IDL) • Chylomicrons (CM). v While the high density lipoprotein considered as a good cholesterol carrier. 2 Normal lipid levels: (Lipids levels are detected in serum after a 12-hour fast) Type of Increased • Cholesterol (C) < 200 mg/dl. Increas hyperlipoproteine lipoprotei Risk • Triglycerides (TG) < 220 mg/dl. ed lipids • Low density lipoprotein (LDL) < 130 mg/dl (bad cholesterol). mia n • High density lipoprotein (HDL) > 50 mg/dl (good cholesterol). Type I CM TGs - Factors promoting elevated blood lipids: Type IIa LDL C Û • VLDL & TG & Family history of coronary artery diseases. Type IIb C Û • Smoking (reduces levels of HDL, cytotoxic effect on the endothelium, increased oxidation of LDL lipoproteins and stimulation of thrombogenesis).
    [Show full text]