Cholesterol Ester Storage Disease

Wolman Disease

Sterol Esterase

Cholesterol Esters

Lipid Metabolism, Inborn Errors

Lipase

Lysosomes

Donald S. Fredrickson

List of diseases (C)

Cholesteryl ester

High-density lipoprotein

Acid lipase disease

List of MeSH codes (C18)

List of MeSH codes (C16)

Lipase a, lysosomal acid type

Lysosomal acid lipase deficiency

Stanol ester

Hyperlipidemia

Lysosomal lipase

Aramchol

Cholesterol

Fat

Beta-propeller

Hypertriglyceridemia

Lipoprotein

Lipoxygenase

Fish oil

Lipid droplet

Adrenal gland

Biochemistry

Niacin

Metabolism

Olive oil

Fatty acid

Lauric acid

Vernix caseosa

Polysaccharide

Milk

Coherent Raman scattering microscopy

Carotenoid

Meat

Lipid

Sulfatide

Anabolic steroid

Trans fat

Cholesteryl esters8

• Lysosomal Acid Lipase (LAL) Deficiency is a rare autosomal recessive lysosomal storage disorder (LSD) that is caused by a marked decrease of lysosomal acid lipase (LAL), the enzyme that breaks down cholesteryl esters and triglycerides in the lysosomes. (clinicaltrials.gov)
• Deficient LAL enzyme activity results in the lysosomal accumulation of cholesteryl esters and triglycerides. (clinicaltrials.gov)
• Lysosomal acid lipase (LAL) is essential for the intracellular degradation of cholesteryl esters (CE) and triacylglycerols (TG) that are delivered to lysosomes by low density lipoprotein (LDL) receptor mediated endocytosis. (zhangqiaokeyan.com)
• Our results show a significant difference between human and mouse LAL in their specificity toward cholesteryl esters. (zhangqiaokeyan.com)
• The lysosomal acid lipase enzyme breaks down lipids such as cholesteryl esters and triglycerides. (medlineplus.gov)
• Decreased lysosomal acid lipase activity results in the accumulation of cholesteryl esters, triglycerides, and other lipids within lysosomes, causing fat buildup in multiple tissues. (medlineplus.gov)
• Cholesteryl esters are made up of two lipids that are attached to each other, cholesterol and a fatty acid. (nih.gov)
• Liver histopathology typically reveals microvesicular steatosis (cytoplasmic lipid vesicles stained by Oilred, Sudan black, Sudan IV), lysosomal accumulation of cholesteryl esters, and TG, along with Maltese cross-type birefringent needle-shaped cholesteryl ester crystals in frozen sections. (edu.mk)

Triglycerides5

• Triglycerides are fatty acid esters of glycerol that have three hydroxyl groups. (cdc.gov)
• Lipoproteins are particles that carry fats such as cholesterol and triglycerides through the blood stream. (nih.gov)
• cholesterol esters and triglycerides, significantly impacts cellular function. (ox.ac.uk)
• Severe infantile phenotype includes hepatosplenomegaly, malabsorption, adrenal calcifications and psychomotor regression, while patients with residual enzyme activity are usually recognized due to chronic hepatosplenomegaly with associated laboratory abnormalities: elevated serum low density lipoprotein (LDL) cholesterol and triglycerides (TG), low serum high density lipoprotein (HDL) cholesterol and moderately elevated serum transaminases (5-9). (edu.mk)
• Hyperlipidemia is a set of metabolic disorders that can be genetic or acquired that are characterized by excess lipids in the blood which can include cholesterol and/or triglycerides. (igenomix.fr)

Accumulation4

• In the liver, this accumulation leads to hepatomegaly, increased hepatic fat content, transaminase elevation signaling chronic liver injury, and progression to fibrosis, cirrhosis, and complications of end stage liver disease. (clinicaltrials.gov)
• A second form of successful enzyme replacement therapy was established for Gaucher disease, an inherited deficiency of lysosomal acid β-glucocerebrosidase that leads to accumulation of the substrate (glucocerebroside and its other breakdown products such as ceramide) in lysosomes. (nih.gov)
• It is characterized by the accumulation of neutral lipids, particularly CHOLESTEROL ESTERS in leukocytes, fibroblasts, and hepatocytes. (nih.gov)
• Niemann-Pick disease is a group of autosomal recessive disorders caused by an accumulation of fat and cholesterol in cells of the liver, spleen, bone marrow, lungs, and, in some instances, brain. (nih.gov)

Lipids13

• Donald S. Fredrickson was a leading scientist investigating the links between lipids and heart disease at a time when the study of lipid transport in the blood emerged as a new field of clinical research. (nih.gov)
• Lipids, which include fats and cholesterol, are easily stored in the body, where they serve as a source of energy and are an important element in the structure of cells. (nih.gov)
• In addition, Dr. Fredrickson discovered two genetic diseases related to the storage of lipids in the body. (nih.gov)
• Until the early 1950s, abnormal plasma lipids were characterized as one of two conditions, either as too much cholesterol (hypercholesterolemia) or as an excess of another component of lipoproteins, trygliceride (hypertrygliceridemia). (nih.gov)
• His interest in lipids led Fredrickson to the discovery of two related diseases linked to the disorders in the metabolism of lipids and lipoproteins. (nih.gov)
• Lipid storage diseases (also known as lipidoses) are a group of inherited metabolic disorders in which harmful amounts of fatty materials (lipids) accumulate in various cells and tissues in the body. (nih.gov)
• Fredrickson's studies of the connection between lipid metabolism (the processing of lipids, chief among them fats and cholesterol, in the body) and heart disease made him one of the most widely cited physiologists of the 1960s and 1970s. (nih.gov)
• In affected individuals, harmful amounts of fats (lipids) accumulate in cells and tissues throughout the body, which typically causes liver disease. (medlineplus.gov)
• The lipids produced through these processes, cholesterol and fatty acids, are used by the body or transported to the liver for removal. (medlineplus.gov)
• The body's inability to produce cholesterol from the breakdown of these lipids leads to an increase in alternative methods of cholesterol production and higher-than-normal levels of cholesterol in the blood. (medlineplus.gov)
• In eutherians, the placenta plays a critical role in the uptake, storage, and metabolism of lipids. (inra.fr)
• Whereas lipid droplets are essential for the storage of neutral lipids in the placenta and many other tissues, the processes that regulate placental lipid droplet lipolysis remain largely unknown. (inra.fr)
• Hyperlipidemia is a general term used to identify a disease associated with excess lipids and/or fats in the body and h ypercholesterolemia is one of the most common forms of hyperlipidemia. (igenomix.fr)

Hydrolase3

• Mechanisms producing the divergent phenotypes, Wolman disease (WD) and cholesterol ester storage disease (CESD), associated with the genetic deficiency of human lysosomal acid lipase/cholesterol ester hydrolase (hLAL) function were investigated with the determination of HLAL activity levels, mRNA and protein expression, and defects in structural gene sequences in cells from three WD and five CESD patients. (nih.gov)
• The acid cholesteryl ester hydrolase activity in the tissues appeared to be normal. (nih.gov)
• Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5) NCIE2 functions as an acyltransferase for the synthesis of phosphatidic acid, the major intermediate in membrane and storage lipid biosynthesis. (inra.fr)

Acid Lipase Def7

• Lysosomal Acid Lipase Deficiency presenting in infants (historically called Wolman Disease) is a medical emergency with rapid disease progression over a period of weeks that is typically fatal within the first 6 months of life. (clinicaltrials.gov)
• Subsequently, similar or related approaches have been taken to treat other enzyme deficiency syndromes such as adenosine deaminase deficiency, lysosomal acid lipase deficiency, Fabry disease, Pompe disease, Hurler and Hunter syndrome and several of the rarer forms of mucopolysaccharidoses. (nih.gov)
• Lysosomal acid lipase deficiency is an inherited condition characterized by problems with the breakdown and use of fats and cholesterol in the body (lipid metabolism). (medlineplus.gov)
• Individuals with this form of lysosomal acid lipase deficiency may have increased liver enzymes and high cholesterol levels, which can be detected with blood tests. (medlineplus.gov)
• 14. Lysosomal acid lipase deficiency impairs regulation of ABCA1 gene and formation of high density lipoproteins in cholesteryl ester storage disease. (nih.gov)
• Cholesteryl ester storage disease: protean presentations of lysosomal acid lipase deficiency. (nih.gov)
• Two types of lysosomal acid lipase deficiency (LAL-D) were recognized: early onset form (Wolman s disease) and late-onset type (cholesteryl ester storage disease - CESD) (3). (edu.mk)

Esterase1

• The low cholesteryl esterase activity does not result in reduced LDL-cholesterol ester degradation in mouse fibroblasts in situ. (zhangqiaokeyan.com)

CESD1

• More commonly, LAL Deficiency presents in children and adults and this presentation has been historically called Cholesteryl Ester Storage Disease (CESD). (clinicaltrials.gov)

Lipase10

• The first of these was cholesterol ester storage disease, the result of a deficiency of a fat-splitting enzyme called acid lipase. (nih.gov)
• Plasma cholesterol levels greater than 200 mg/dl or less than 120 mg/dl - includes patients with diagnoses such as familial hypercholesterolemia, familial combined hyperlipidemia, sitosterolemia, cholesteryl ester storage disease, Erdheim chester disease, lipoprotein lipase, hepatic lipase or apo-CII deficiency, and dysbetalipoproteinemia. (nih.gov)
• Plasma HDL-C levels greater than 70 mg/dl or less than 25 mg/dl - includes patients with deficiency of cholesteryl ester transfer protein, lecithin cholesterol acyltransferase, phospholipid transfer protein, lipoprotein lipase, hepatic lipase, or apo-CII, and Tangier disease. (nih.gov)
• BACKGROUND: Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. (ox.ac.uk)
• KANUMA ® is a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency. (nih.gov)
• Lysosomal acid lipase separates the cholesterol from the fatty acid. (nih.gov)
• Endogenous TG are synthesized in hepatocytes, where jointly with cholesterol and apolipoproteins (apoB 100, apoE, apoC) constitute building material for VLDL secreted into the blood, where their remnants (IDL) are formed by an action of endothelial lipase (EL). (archivesofmedicalscience.com)
• LDL are formed from IDL with the involvement of hepatic lipase (HL) and are enriched with HDL cholesterol, with the involvement of the cholesterol ester transfer protein (CETP) [ 1 - 3 ]. (archivesofmedicalscience.com)
• ABCA1 - ATP-binding cassette transporter A1, CETP - cholesterol ester transfer protein, EL - endothelial lipase, HL - hepatic lipase, LCAT - lecithin cholesterol acyltransferase, LPL - lipoprotein lipase, PLTP - phospholipid transfer protein, TG - triglycerides. (archivesofmedicalscience.com)
• It lowers circulating triglyceride levels by activating lipoprotein lipase which is a key enzyme in the degradation of VLDL (very low density lipoprotein) cholesterol. (medicineindia.org)

Deficiency6

• In general, data on the prevalence of LAL Deficiency are limited, and the overall prevalence of the disease in the population is unclear. (clinicaltrials.gov)
• In addition to liver disease, patients with LAL Deficiency experience increased risk for cardiovascular disease and accelerated atherosclerosis. (clinicaltrials.gov)
• The LAL Deficiency Registry is a global registry, established to help improve care for patients through improved understanding of the disease and long-term effectiveness of therapeutic interventions including sebelipase alfa. (clinicaltrials.gov)
• Gaucher disease is caused by a deficiency of the enzyme glucocerebrosidase. (nih.gov)
• Niemann-Pick disease type C is not caused by a deficiency of sphlingomyelinase but by a lack of the NPC1 or NPC2 proteins. (nih.gov)
• A recessively inherited, progressive lysosomal storage disease caused by a deficiency of GLYCOSYLASPARAGINASE activity. (bvsalud.org)

Lysosomes1

• Disorders in which intracellular material that cannot be metabolized is stored in lysosomes are called lysosomal storage diseases. (nih.gov)

Phospholipid transfer protein1

• 13. Absence of endogenous phospholipid transfer protein impairs ABCA1-dependent efflux of cholesterol from macrophage foam cells. (nih.gov)

Wolman Disease6

• Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease. (ox.ac.uk)
• RESULTS: We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT-multimodal therapy. (ox.ac.uk)
• CONCLUSION: We describe combined ERT, DSR and HCT, multimodal treatment for Wolman disease. (ox.ac.uk)
• Multimodal therapy should be considered a new paradigm of treatment for Wolman disease patients where there is an attenuated response to ERT, and for all patients where there is a well-matched transplant donor, in order to improve long term gut function, tolerance of a normal diet and quality of life. (ox.ac.uk)
• The early-onset form was known as Wolman disease, and the later-onset form was known as cholesteryl ester storage disease. (medlineplus.gov)
• Saito S, Ohno K, Suzuki T, Sakuraba H. Structural bases of Wolman disease and cholesteryl ester storage disease. (nih.gov)

Fats and cholesterol1

• His system of classifying disorders in lipid metabolism was adopted by the World Health Organization as an international standard for identifying increased risks of coronary artery disease, heart attack, and stroke linked to the consumption of fats and cholesterol. (nih.gov)

Coronary heart d3

• They are also thought to contribute to coronary heart disease if consumed and stored in excess. (nih.gov)
• Some forms of lipoproteins, called high-density lipoproteins (HDL), carry cholesterol out of the blood stream to the liver for excretion in the bile, and have been shown to reduce the risk of premature coronary heart disease. (nih.gov)
• This clinical trial offered conclusive evidence that reduction of cholesterol in the blood alone can prevent heart attack and death due to coronary heart disease. (nih.gov)

Cardiovascular disease6

• and 2) to evaluate prevention and treatment programs targeting cardiovascular disease in the U.S. (cdc.gov)
• The main element of the cardiovascular disease laboratory component in NHANES is blood lipid levels. (cdc.gov)
• Cardiovascular disease is the leading cause of death in the United States. (cdc.gov)
• The main risks are those of excessive androgens: menstrual irregularities and virilization in women and impotence, premature cardiovascular disease and prostatic hypertrophy in men. (inchem.org)
• Known cardiovascular disease is a relative contraindication. (inchem.org)
• A 2016 review of coconut oil (which is nearly half Dodecoic acid) was similarly inconclusive about the effects on cardiovascular disease risk. (ataman-chemicals.com)

Gene1

• 189 disease terms (MeSH) has been reported with APOB gene. (cdc.gov)

Tissues2

• Another group of patients, the first of whom came from Tangier Island in the Chesapeake Bay in 1960, showed prominent deposits of cholesterol in body tissues, especially in greatly-enlarged tonsils, which accumulated due to a lack of high-density lipoproteins that help eliminate cholesterol from the body. (nih.gov)
• Supply of cholesterol to the peripheral tissues, where it is essential for the formation of cell membranes and biosynthesis of steroid hormones, and to the liver, where it is used for the synthesis of bile acids ( hepatic pathway ) ( Figure 2 ). (archivesofmedicalscience.com)

Gaucher3

• Subsequently, recombinant forms of glucocerebrosidase have been developed and now constitute the standard of care for type 1 Gaucher disease. (nih.gov)
• Type 2 (acute infantile neuropathic Gaucher disease) typically begins within three months of birth. (nih.gov)
• It is characterized by slowly progressive yet milder neurologic symptoms compared to type 2 Gaucher disease. (nih.gov)

High cholesterol1

• Its high cholesterol content had raised sudden concerns about this dietary staple. (nih.gov)

Disorders4

• The diseases treated are generally rare genetic disorders which lead to severe disability and premature death. (nih.gov)
• He also discovered two diseases, cholesterol ester storage disease and Tangier Disease, caused by genetic disorders in the storage of cholesterol in the body. (nih.gov)
• Pathogenic variants in LIPA cause a rare autosomal-recessive disease belonging to the family of lysosomal storage disorders (LSDs) (2). (edu.mk)
• Obesity and hyperlipidemia are known to be risk factors for various pathological disorders, including various forms of infectious respiratory disease, including the current Coronavirus outbreak termed Coronavirus Disease 19 (COVID-19). (mdpi.com)

Serum5

• Serum LDL-cholesterol levels were derived on examinees that were examined in the morning session only. (cdc.gov)
• The distribution of serum LDL-cholesterol should be estimated only on examinees aged 12 and above who fasted at least 8.5 hours or more but less than 24 hours in the morning session. (cdc.gov)
• Dodecoic acid increases total serum cholesterol more than many other fatty acids, but mostly high-density lipoprotein (HDL) (the "good" blood cholesterol). (ataman-chemicals.com)
• In general, a lower total/HDL serum cholesterol ratio correlates with a decrease in atherosclerotic risk. (ataman-chemicals.com)
• Nonetheless, an extensive meta-analysis on foods affecting the total LDL/serum cholesterol ratio found in 2003 that the net effects of Dodecoic acid on coronary artery disease outcomes remained uncertain. (ataman-chemicals.com)

Fatty acids1

• Dietary TG are hydrolysed in the intestine into free fatty acids (FFA), mono- and diglycerides, absorbed with the exogenous cholesterol by enterocytes, in which CM that transport them are formed and subsequently enter the circulation through the lymphatic system. (archivesofmedicalscience.com)

Phenotype1

• 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. (ox.ac.uk)

Lipid storage1

• The tonsils proved to be only the most visible markers of wide spread lipid storage throughout the reticuloendothelial system. (nih.gov)

APOE1

• 17. Proteomic analysis of HDL from inbred mouse strains implicates APOE associated with HDL in reduced cholesterol efflux capacity via the ABCA1 pathway. (nih.gov)

Abnormalities2

• Each also responded to different diets or drugs, important information for physicians and nutritionists newly aware of the dangers of cholesterol abnormalities. (nih.gov)
• By the time he became Clinical Director of the National Heart Institute and Head of its Section on Molecular Diseases in 1961, Fredrickson had concentrated on the study of hereditary abnormalities in plasma lipoproteins, a new discipline he called Genetic Dyslipoproteinemia. (nih.gov)

Cassette transporter1

• 10. Statin-induced decrease in ATP-binding cassette transporter A1 expression via microRNA33 induction may counteract cholesterol efflux to high-density lipoprotein. (nih.gov)

ABCA16

• 2. HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular cholesterol export. (nih.gov)
• 4. ABCA1-dependent mobilization of lysosomal cholesterol requires functional Niemann-Pick C2 but not Niemann-Pick C1 protein. (nih.gov)
• 6. Impaired ABCA1-dependent lipid efflux and hypoalphalipoproteinemia in human Niemann-Pick type C disease. (nih.gov)
• 7. The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease. (nih.gov)
• 8. ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity. (nih.gov)
• 9. Common ABCA1 variants, HDL levels, and cellular cholesterol efflux in subjects with familial low HDL. (nih.gov)

Enzyme replace1

• A list of enzymes approved for use in enzyme replacement therapy in the United States, the year of first approval, the generic and brand names of the product and the disease for which they are used are given in the Table. (nih.gov)

TANGIER DISEASE3

• Fredrickson named this condition Tangier disease. (nih.gov)
• He concluded that both cholesterol ester storage disease and Tangier disease were hereditary in origin. (nih.gov)
• 2. The tonsils of a patient with Tangier disease. (nih.gov)

MeSH1

• Lysosomal Storage Diseases, Nervous System" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (sdsu.edu)

Lipoproteins4

• Other lipoproteins, called low-density proteins (LDL), deposit cholesterol within arteries and are thought to increase the risk of heart disease. (nih.gov)
• have been engaged for about 20 years in the study of plasma lipoproteins and the diseases that affect them. (nih.gov)
• 16. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. (nih.gov)
• Lipoproteins are a family of large particles composed of an "envelope", which contains phospholipids and free cholesterol, and a core containing TG and cholesterol esters. (archivesofmedicalscience.com)

Cellular1

• Over time, excessive storage of fats can cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system (the nerves from the spinal cord to the rest of the body), liver, spleen, and bone marrow. (nih.gov)

Hyperlipidemia1

• The data will be used to monitor the status of hyperlipidemia and the success of the National Cholesterol Education Program. (cdc.gov)

Diabetes Mellitus1

• Diabetes mellitus, as one of the most challenging chronic diseases, currently affects over 387 million people worldwide and this number is estimated to increase to around 500 million by 2030 (J. E. Shaw et al. (justia.com)

Liver disease2

• Scar tissue quickly builds up in the liver, leading to liver disease (cirrhosis). (medlineplus.gov)
• they accumulate in the liver, resulting in liver disease. (nih.gov)

Genes2

• 18. HDL activates expression of genes stimulating cholesterol efflux in human monocyte-derived macrophages. (nih.gov)
• It provides a comprehensive analysis of the genes involve d in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved. (igenomix.fr)

OMIM1

• from OMIM) By examining the critical region for triglyceride storage disease with impaired long-chain fatty acid oxidation, a rare autosomal recessive form of NCIE (242100), on chromosome 3p21, Lefevre et al. (inra.fr)