keyword
MENU ▼
Read by QxMD icon Read
search

Lysosomal storage disorders, Lysosomal acid lipase deficiency

keyword
https://www.readbyqxmd.com/read/27624512/lysosomal-acid-lipase-deficiency-unmasked-in-two-children-with-nonalcoholic-fatty-liver-disease
#1
Ryan W Himes, Sarah E Barlow, Kevin Bove, Norma M Quintanilla, Rachel Sheridan, Rohit Kohli
Lysosomal acid lipase deficiency (LAL-D) is a classic lysosomal storage disorder characterized by accumulation of cholesteryl ester and triglyceride. Although it is associated with progressive liver injury, fibrosis, and end-stage liver disease in children and adolescents, LAL-D frequently presents with nonspecific signs that overlap substantially with other, more common, chronic conditions like nonalcoholic fatty liver disease (NAFLD), metabolic syndrome, and certain inherited dyslipidemias. We present 2 children with NAFLD who achieved clinically significant weight reduction through healthy eating and exercise, but who failed to have the anticipated improvements in aminotransferases and γ-glutamyl transferase...
September 13, 2016: Pediatrics
https://www.readbyqxmd.com/read/27392817/successful-long-term-outcome-of-liver-transplantation-in-late-onset-lysosomal-acid-lipase-deficiency
#2
S Sreekantam, I Nicklaus-Wollenteit, J Orr, K Sharif, S Vijay, P J McKiernan, S Santra
Late-onset LAL deficiency, previously referred to as cholesteryl ester storage disorder, is a rare lysosomal storage disorder characterized by accumulation of cholesteryl esters. It has a heterogeneous clinical phenotype including abdominal pain, poor growth, hyperlipidemia with vascular complications and hepatosplenomegaly. End-stage liver disease may occur, but there are few reports of successful LT. There are also concerns that systemic manifestations of the disease might persist post-LT. We report a case with excellent outcome eight yr following LT...
September 2016: Pediatric Transplantation
https://www.readbyqxmd.com/read/26849851/novel-therapies-for-severe-dyslipidemia-originating-from-human-genetics
#3
Daniel Gaudet
PURPOSE OF REVIEW: Novel therapies for severe dyslipidemia target a wide range of unmet medical needs: severe familial hypercholesterolemia, severe hypertriglyceridemia and chylomicronemia, elevated lipoprotein (a), lipodystrophies, high-density lipoprotein particle diseases, lysosomal acid lipase deficiency and storage diseases, nonalcoholic fatty liver disease and others. The purpose of this review is to describe the contribution of human genetics to the development of therapeutic approaches targeting severe dyslipidemia...
April 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/26385844/cholesterol-ester-storage-disease-with-a-novel-lipa-mutation-l264p-that-presented-massive-hepatomegaly-a-case-report
#4
Naomi Kuranobu, Jun Murakami, Ken Okamoto, Rei Nishimura, Kei Murayama, Ayumi Takamura, Toshiko Umeda, Yoshikatsu Eto, Susumu Kanzaki
Cholesterol ester storage disease (CESD) is an autosomal recessive disorder caused by deficient lysosomal acid lipase (LAL) activity, resulting in cholesteryl ester (CE) accumulation. CESD patients have liver disease associated with mixed dyslipidemia leading to liver failure. We here report the case of an 11-year-old male CESD patient with a novel mutation who had the chief complaint of massive hepatomegaly. The patient's liver reached to his pelvis, and his spleen was 2 cm below the costal margin. The patient had elevated serum liver enzymes and mixed dyslipidemia...
March 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/26283692/prd125-a-potent-and-selective-inhibitor-of-sterol-o-acyltransferase-2-markedly-reduces-hepatic-cholesteryl-ester-accumulation-and-improves-liver-function-in-lysosomal-acid-lipase-deficient-mice
#5
Adam M Lopez, Jen-Chieh Chuang, Kenneth S Posey, Taichi Ohshiro, Hiroshi Tomoda, Lawrence L Rudel, Stephen D Turley
In most organs, the bulk of cholesterol is unesterified, although nearly all possess a varying capability of esterifying cholesterol through the action of either sterol O-acyltransferase (SOAT) 1 or, in the case of hepatocytes and enterocytes, SOAT2. Esterified cholesterol (EC) carried in plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease or cholesteryl ester storage disease (CESD)...
November 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/26065284/-lysosomal-acid-lipase-deficiency-in-children-our-experience-and-a-novel-possibility-of-enzyme-replacement-therapy
#6
Danijela Petković Ramadža, Mario Ćuk, Karin Zibar, Marina Barić, Vladimir Sarnavka, Karmen Bilić, Ksenija Fumić, Jurica Vuković, Silvija Pušeljić, Marijana Ćorić, Ranka Štern Padovan, Marko Kralik, Ivo Barić
Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression...
March 2015: Lijec̆nic̆ki Vjesnik
https://www.readbyqxmd.com/read/25450374/deletion-of-sterol-o-acyltransferase-2-soat2-function-in-mice-deficient-in-lysosomal-acid-lipase-lal-dramatically-reduces-esterified-cholesterol-sequestration-in-the-small-intestine-and-liver
#7
Adam M Lopez, Kenneth S Posey, Stephen D Turley
Sterol O-acyltransferase 2 (SOAT2), also known as ACAT2, is the major cholesterol esterifying enzyme in the liver and small intestine (SI). Esterified cholesterol (EC) carried in certain classes of plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease (WD) or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders...
November 7, 2014: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25345094/lysosomal-acid-lipase-deficiency-diagnosis-and-treatment-of-wolman-and-cholesteryl-ester-storage-diseases
#8
REVIEW
Anthony F Porto
Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesterol esters and triglycerides. LAL is coded by the LIPA gene on chromosome 10q23.31. Its deficiency leads to two autosomal recessive disorders, Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD). WD has an estimated incidence of 1 in 500,000 live births and is the result of a complete loss of LAL and presents in infancy with vomiting, diarrhea, poor weight gain and hepatomegaly subsequently leading to death. CESD is the result of partial loss of LAL and its presentation is more variable...
September 2014: Pediatric Endocrinology Reviews: PER
https://www.readbyqxmd.com/read/25234559/jcl-roundtable-enzyme-replacement-therapy-for-lipid-storage-disorders
#9
W Virgil Brown, Robert J Desnick, Gregory A Grabowski
There are several inherited disorders that involve abnormal storage of lipids in tissues leading to severe compromise of organs. Sadly, these are often accompanied by lifelong morbidity and early mortality. Disorders such as Gaucher, Fabry, and lysosomal acid lipase deficiencies (Wolman and cholesteryl ester storage diseases) have been known for many years, and provide a difficult and frustrating set of problems for patients, their families, and their physicians. With recombinant methods of protein synthesis, it is now possible to literally replace the defective enzymes that underlie the basic pathophysiology of many such disorders...
September 2014: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/24832708/infant-case-of-lysosomal-acid-lipase-deficiency-wolman-s-disease
#10
Meghmala Sadhukhan, Amit Saha, Roshni Vara, Bim Bhaduri
Lysosomal acid lipase (LAL) deficiency is a rare autosomal recessive disorder which causes two distinct clinical phenotypes: Wolman's disease and cholesterol ester storage disease. LAL hydrolyses LDL-derived triglycerides and cholesterol esters to glycerol or cholesterol and free fatty acids. Its deficiency leads to accumulation of intracellular triglycerides and/or cholesterol esters. In early onset LAL deficiency, clinical manifestations start in the first few weeks of life with persistent vomiting, failure to thrive, hepatosplenomegaly, liver dysfunction and hepatic failure...
2014: BMJ Case Reports
https://www.readbyqxmd.com/read/24798600/lysosomal-acid-lipase-deficiency-wolman-disease-and-cholesteryl-ester-storage-disease
#11
REVIEW
Anna Tylki-Szymańska, Agnieszka Jurecka
Cholesteryl ester storage disease (CESD, OMIM #278000) and Wolman disease (OMIM #278000) are autosomal recessive lysosomal storage disorders caused by a deficient activity of lysosomal acid lipase (cholesteryl ester hydrolase, LAL). Human lysosomal acid lipase is essential for the metabolism of cholesteryl esters and triglycerides. In Wolman disease, LAL activity is usually absent, whereas CESD usually presents some residual LAL activity. In infants, poor weight gain, massive hepatosplenomegaly, calcified adrenal glands (present about 2/3 of the time), vomiting, diarrhea and failure to thrive are indicative of Wolman disease...
2014: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/24508470/extended-use-of-a-selective-inhibitor-of-acid-lipase-for-the-diagnosis-of-wolman-disease-and-cholesteryl-ester-storage-disease
#12
G Civallero, J De Mari, C Bittar, M Burin, R Giugliani
Lysosomal acid lipase (LAL) deficiency produces two well defined inborn disorders, Wolman disease (WD) and cholesteryl ester storage disease (CESD). WD is a severe, early-onset condition involving massive storage of triglycerides and cholesteryl esters in the liver, with death usually occurring before one year of life. CESD is a more attenuated, later-onset disease that leads to a progressive and variable liver dysfunction. Diagnosis of LAL deficiency is mainly based on the enzyme assay of LAL activity in fibroblasts...
April 10, 2014: Gene
https://www.readbyqxmd.com/read/24122380/cholesteryl-ester-storage-disease-an-easily-missed-diagnosis-in-oligosymptomatic-children
#13
F Freudenberg, P Bufler, R Ensenauer, P Lohse, S Koletzko
Cholesteryl ester storage disease (CESD) is a rare, autosomal recessively inherited disorder resulting from deficient activity of lysosomal acid lipase (LAL). LAL is the key enzyme hydrolyzing cholesteryl esters and triglycerides stored in lysosomes after LDL receptor-mediated endocytosis. Mutations within the LIPA gene locus on chromosome 10q23.2-q23.3 may result either in the always fatal Wolman disease, where no LAL activity is found, or in the more benign disorder CESD with a reduced enzymatic activity, leading to massive accumulation of cholesteryl esters and triglycerides in many body tissues...
October 2013: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/23652569/lysosomal-acid-lipase-a-and-the-hypercholesterolaemic-phenotype
#14
Sigrid W Fouchier, Joep C Defesche
PURPOSE OF REVIEW: Mutations in lysosomal acid lipase A (LIPA) result in two phenotypes depending on the extent of lysosomal acid lipase (LAL) deficiency: the severe, early-onset Wolman disease or the less severe cholesteryl ester storage disease (CESD). In CESD, the severity of the symptoms, hepatomegaly and hypercholesterolaemia, can be highly variable, presenting in childhood or adulthood. Therefore, it is likely that many patients are undiagnosed or misdiagnosed. Nevertheless, LAL deficiency has been recognized for more than 25 years, but adequate therapeutic strategies are limited...
August 2013: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/23624251/hepatic-cholesteryl-ester-accumulation-in-lysosomal-acid-lipase-deficiency-non-invasive-identification-and-treatment-monitoring-by-magnetic-resonance
#15
MULTICENTER STUDY
Peter E Thelwall, Fiona E Smith, Mark C Leavitt, David Canty, Wei Hu, Kieren G Hollingsworth, Christian Thoma, Michael I Trenell, Roy Taylor, Joseph V Rutkowski, Andrew M Blamire, Anthony G Quinn
BACKGROUND & AIMS: Lysosomal Acid Lipase (LAL) deficiency is a rare metabolic storage disease, caused by a marked reduction in activity of LAL, which leads to accumulation of cholesteryl esters (CE) and triglycerides (TG) in lysosomes in many tissues. We used (1)H magnetic resonance (MR) spectroscopy to characterize the abnormalities in hepatic lipid content and composition in patients with LAL deficiency, and in ex vivo liver tissue from a LAL deficiency rat model. Secondly, we used MR spectroscopy to monitor the effects of an enzyme replacement therapy (ERT), sebelipase alfa (a recombinant human lysosomal acid lipase), on hepatic TG and CE content in the preclinical model...
September 2013: Journal of Hepatology
https://www.readbyqxmd.com/read/23425886/meeting-report-rare-disease-in-south-eastern-europe-15-17-november-2012-skopje-republic-of-macedonia
#16
Z Gucev, V Tasic, M Polenakovic
(Full text is available at http://www.manu.edu.mk/prilozi).Under the auspices of the European Academy of Paediatrics, the first Rare Disease in South-Eastern Europe (SEE) meeting was held on November 15-17 2012, at the Macedonian Academy of Sciences and Arts, Skopje (MASA). This was a manifestation in honour of the 45 years since its establishment, under the guidance of the G.D. Efremov Research Centre for Genetic Engineering and Bio-technology. The Macedonian Chamber of Doctors granted 20 CME credit points for the meeting...
December 2012: Prilozi
https://www.readbyqxmd.com/read/23424026/frequency-of-the-cholesteryl-ester-storage-disease-common-lipa-e8sjm-mutation-c-894g-a-in-various-racial-and-ethnic-groups
#17
COMPARATIVE STUDY
Stuart A Scott, Benny Liu, Irina Nazarenko, Suparna Martis, Julia Kozlitina, Yao Yang, Charina Ramirez, Yumi Kasai, Tommy Hyatt, Inga Peter, Robert J Desnick
UNLABELLED: Cholesteryl ester storage disease (CESD) and Wolman disease are autosomal recessive later-onset and severe infantile disorders, respectively, which result from the deficient activity of lysosomal acid lipase (LAL). LAL is encoded by LIPA (10q23.31) and the most common mutation associated with CESD is an exon 8 splice junction mutation (c.894G>A; E8SJM), which expresses only ∼3%-5% of normally spliced LAL. However, the frequency of c.894G>A is unknown in most populations...
September 2013: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/23233555/gaucher-disease-and-other-storage-disorders
#18
REVIEW
Gregory A Grabowski
In 1882, Philippe Gaucher described a 32-year-old woman with massive splenomegaly and unusually large cells in the spleen, which he called a "primary epithelioma of the spleen." The systemic nature and inheritance of the disease and its variants involving the viscera and CNS were described over the next century. The delineation of the causal enzymatic defects, genetics, molecular pathology, and genomics have provided pathogenic insights into the phenotypic spectrum and the bases for development of specific therapies for what is now known as Gaucher disease...
2012: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/23035117/%C3%AE-tocopherol-reduces-lipid-accumulation-in-niemann-pick-type-c1-and-wolman-cholesterol-storage-disorders
#19
Miao Xu, Ke Liu, Manju Swaroop, Forbes D Porter, Rohini Sidhu, Sally Firnkes, Sally Finkes, Daniel S Ory, Juan J Marugan, Jingbo Xiao, Noel Southall, William J Pavan, Cristin Davidson, Steven U Walkley, Alan T Remaley, Ulrich Baxa, Wei Sun, John C McKew, Christopher P Austin, Wei Zheng
Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts...
November 16, 2012: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22960355/drug-induced-phospholipidosis-an-acquired-lysosomal-storage-disorder
#20
REVIEW
James A Shayman, Akira Abe
There is a strong association between lysosome enzyme deficiencies and monogenic disorders resulting in lysosomal storage disease. Of the more than 75 characterized lysosomal proteins, two thirds are directly linked to inherited diseases of metabolism. Only one lysosomal storage disease, Niemann-Pick disease, is associated with impaired phospholipid metabolism. However, other phospholipases are found in the lysosome but remain poorly characterized. A recent exception is lysosomal phospholipase A2 (group XV phospholipase A2)...
March 2013: Biochimica et Biophysica Acta
keyword
keyword
59615
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"