• Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. (wikipedia.org)
  • Lysosomal acid lipase deficiency is a genetic disease that is autosomal recessive. (wikipedia.org)
  • 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)
  • In the severe, early-onset form of lysosomal acid lipase deficiency, lipids accumulate throughout the body, particularly in the liver, within the first weeks of life. (medlineplus.gov)
  • Infants with this form of lysosomal acid lipase deficiency develop multi-organ failure and severe malnutrition and generally do not survive past 1 year. (medlineplus.gov)
  • In the later-onset form of lysosomal acid lipase deficiency, signs and symptoms vary and usually begin in mid-childhood, although they can appear anytime up to late adulthood. (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)
  • Some people with this later-onset form of lysosomal acid lipase deficiency develop an accumulation of fatty deposits on the artery walls ( atherosclerosis ). (medlineplus.gov)
  • Although these deposits are common in the general population, they usually begin at an earlier age in people with lysosomal acid lipase deficiency. (medlineplus.gov)
  • The expected lifespan of individuals with later-onset lysosomal acid lipase deficiency depends on the severity of the associated health problems. (medlineplus.gov)
  • The two forms of lysosomal acid lipase deficiency were once thought to be separate disorders. (medlineplus.gov)
  • Although these two disorders have the same genetic cause and are now considered to be forms of a single condition, these names are still sometimes used to distinguish between the forms of lysosomal acid lipase deficiency. (medlineplus.gov)
  • Lysosomal acid lipase deficiency is estimated to occur in 1 in 40,000 to 300,000 individuals, varying by population. (medlineplus.gov)
  • Mutations in the LIPA gene cause lysosomal acid lipase deficiency. (medlineplus.gov)
  • Mutations in the LIPA gene lead to a shortage (deficiency) of functional lysosomal acid lipase. (medlineplus.gov)
  • Individuals with the early-onset form of lysosomal acid lipase deficiency have no normal enzyme activity. (medlineplus.gov)
  • A rare, progressive metabolic liver disease due to marked to complete lysosomal acid lipase deficiency and characterized by dyslipidemia and massive lipid accumulation leading to hepatomegaly and liver dysfunction, splenomegaly, accelerated atherosclerosis. (orpha.net)
  • Lysosomal acid lipase deficiency (LAL-D), also known as Wolman disease or cholesterol ester storage disease (CESD), is an inherited genetic condition in which the body does not produce enough lysosomal acid lipase enzyme to process fats and cholesterol. (panfoundation.org)
  • Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants ', Genetics in medicine , pp. (cu.edu.eg)
  • Lysosomal acid lipase deficiency is caused by homozygous or compound heterozygous mutation in the LIPA gene. (bredagenetics.com)
  • Lysosomal acid lipase deficiency is predominantly a pediatric disease , although milder forms of the disease with possibility of a normal life-span are also possible. (bredagenetics.com)
  • Deficiency of lysosomal acid lipase causes two distinct phenotypes in humans: Wolman disease and cholesteryl ester storage disease (CESD). (bredagenetics.com)
  • In 2015 the results of a phase 3 trial with sebelipase , a recombinant human lysosomal acid lipase, resulted in a reduction in multiple disease-related hepatic and lipid abnormalities in children and adults with lysosomal acid lipase deficiency. (bredagenetics.com)
  • Subsequently Sebelipase alfa (Kanuma™) , administered by intravenous infusion once weekly or once every other week, received its first global approval, in the EU, in August 2015 for long-term enzyme replacement therapy in patients of all ages with lysosomal acid lipase deficiency deficiency. (bredagenetics.com)
  • Sebelipase alfa injection is used to treat patients with Lysosomal acid lipase (LAL) deficiency. (drugs.com)
  • Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. (austral.edu.ar)
  • Lysosomal acid lipase deficiency (LAL-D) is still a little recognized genetic disease with significant morbidity and mortality in children and adults. (austral.edu.ar)
  • It is recommended to add lysosomal acid lipase deficiency to the List of differential diagnoses of sepsis, oncological diseases, storage diseases, persistent diarrhea, chronic malnutrition, and hemophagocytic lymphohistiocytosis. (austral.edu.ar)
  • On 17 December 2010, orphan designation (EU/3/10/827) was granted by the European Commission to HungaroTrial Ltd, Hungary, for recombinant human lysosomal acid lipase for the treatment of lysosomal acid lipase deficiency. (europa.eu)
  • recombinant human lysosomal acid lipase, sebelipase alfa (Kanuma) has been authorised in the EU since 28 August 2015 for long-term enzyme replacement therapy (ERT) in patients of all ages with lysosomal acid lipase (LAL) deficiency. (europa.eu)
  • Lysosomal acid lipase deficiency is an inherited disease caused by the lack of one of the enzymes needed to break down fats within cells. (europa.eu)
  • Lysosomal acid lipase deficiency is a severe and life-threatening disease which, in its most severe form, is usually fatal in the first year of life. (europa.eu)
  • At the time of designation, lysosomal acid lipase deficiency affected less than 0.2 in 10,000 people in the European Union (EU). (europa.eu)
  • At the time of designation, no satisfactory methods were authorised in the EU for the treatment of lysosomal acid lipase deficiency. (europa.eu)
  • Recombinant human lysosomal acid lipase is an 'enzyme replacement therapy' that is expected to work by replacing the missing enzyme in lysosomal acid lipase deficiency, helping to break down fats and stopping them building up in the body's cells. (europa.eu)
  • At the time of submission of the application for orphan designation , no clinical trials with the medicine in patients with lysosomal acid lipase deficiency had been started. (europa.eu)
  • At the time of submission, recombinant human lysosomal acid lipase was not authorised anywhere in the EU for the treatment of lysosomal acid lipase deficiency. (europa.eu)
  • Strensiq and Kanuma are injected enzyme replacement therapies that treat hypophosphatasia and lysosomal acid lipase deficiency, respectively. (pharmacytimes.com)
  • The drug is designed to treat, lysosomal acid lipase deficiency that causes fat to accumulate in the liver, spleen and vasculature. (isaaa.org)
  • In each disorder, a deficiency of a lysosomal hydrolase is inherited, which leads to lysosomal accumulation of the enzyme's specific sphingolipid substrate. (medscape.com)
  • Dietary restriction has shown promise for disorders such as lysosomal acid lipase deficiency (Wolman disease), as has incorporation of lipid-lowering drugs in the regimen along with sebelipase alpha, a recombinant enzyme replacement therapy. (medscape.com)
  • Today, the U.S. Food and Drug Administration approved Kanuma (sebelipase alfa) as the first treatment for patients with a rare disease known as lysosomal acid lipase (LAL) deficiency. (news-medical.net)
  • Fabry disease (also known as Fabry's disease, Anderson-Fabry disease, angiokeratoma corporis diffusum and alpha-galactosidase A deficiency) is a rare X-linked recessive (inherited) lysosomal storage disease, which can cause a wide range of systemic symptoms. (news-medical.net)
  • Synageva BioPharma Corp., a biopharmaceutical company developing therapeutic products for rare disorders, announced today the submission to the Comisión Federal para la Protección contra Riesgos Sanitarios in Mexico for Kanuma as a treatment for patients with lysosomal acid lipase deficiency (LAL Deficiency), a rare genetic disease with significant morbidity and early mortality. (news-medical.net)
  • In September, Genomenon signed an agreement with Alexion, AstraZeneca Rare Disease to create genetic data sets for a group of rare diseases that includes Wilson disease, complement-mediated thrombotic microangiopathy (CM-TMA), lysosomal acid lipase deficiency (LAL-D) and hypophosphatasia (HPP). (biospace.com)
  • On Dec. 8 the Food and Drug Administration approved a new chicken that has been genetically modified to treat a rare and potentially fatal disorder called lysosomal acid lipase deficiency. (economicpolicyjournal.com)
  • Cholesteryl ester storage disease (CESD) is an autosomal recessive disorder resulting from lysosomal acid lipase deficiency and is usually characterized by hepatomegaly and hyperlipidemia. (turkishjournalpediatrics.org)
  • Detailed Description 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. (cardiff.ac.uk)
  • 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. (cardiff.ac.uk)
  • Drug desensitization procedures may be a safe and effective way to avoid the discontinuation of enzyme replacement therapy in patients with lysosomal storage disorders such as lysosomal acid lipase deficiency (LAL-D) who have previously experienced hypersensitivity reactions, according to an article published in Pediatric Allergy and Immunology . (rarediseaseadvisor.com)
  • The condition is caused by a mutation of the LIPA gene, which encodes the lysosomal lipase protein (also called lysosomal acid lipase or LAL), that results in a loss of the protein's normal function. (wikipedia.org)
  • Lysosomal acid lipase deficiencies occur when a person has defects (mutations) in both copies of the LIPA gene. (wikipedia.org)
  • The LIPA gene provides instructions for producing an enzyme called lysosomal acid lipase. (medlineplus.gov)
  • The disease is due to mutations in the gene LIPA (10q23.2-q23.3) encoding the enzyme lysosomal acid lipase (LAL). (orpha.net)
  • Recombinant human lysosomal acid lipase is produced by a method known as 'recombinant DNA technology': it is extracted from the eggs of hens that have been given genes that make them able to produce an exact copy of the human enzyme in their eggs. (europa.eu)
  • The effects of recombinant human lysosomal acid lipase have been evaluated in experimental models. (europa.eu)
  • Progressive lysosomal lipid accumulation leads to the characteristic liver pathology and dysfunction (including hepatomegaly, liver fibrosis and/or cirrhosis, and elevated serum transaminases), dyslipidemia (elevated serum LDL-cholesterol and triglycerides, with normal to low HDL-cholesterol concentrations), premature atherosclerosis, splenomegaly and, eventually, end-stage liver failure. (orpha.net)
  • [ 1 , 2 ] Lipid substrates share a common structure, including a ceramide backbone (2- N -acyl-sphingosine), in which various sphingolipids are derived by substitution of hexoses, phosphorylcholine, or one or more sialic acid residues on terminal hydroxyl groups of the ceramide molecule. (medscape.com)
  • New research on the blood lipid-lowering protein FGF21 shows how it redistributes fatty acids by two distinct mechanisms. (news-medical.net)
  • Lipid nanoparticles (SLNs and NLCs) are regarded as highly promising systems for delivering nucleic acids in gene therapy. (news-medical.net)
  • This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). (cancerindex.org)
  • We have identified a novel class of peptides bound to MHC class II: mannose 6- phosphate (Man-6-P) containing glycopeptides from lysosomal enzymes. (ox.ac.uk)
  • More recently, the concept of lysosomal storage disease has been expanded to include deficiencies or defects in proteins necessary for the normal post-translational modification of lysosomal enzymes (which themselves are often glycoproteins), activator proteins, or proteins important for proper intracellular trafficking between the lysosome and other intracellular compartments. (medscape.com)
  • Lysosomal enzymes then degrade the cargo contained within the autolysosome. (hindawi.com)
  • Observing the changes of activity of some lysosomal enzymes in blood serum of female rabbits subjected to injection of 10 microg of ghrelin/kg of body weight. (nel.edu)
  • Changes of lysosomal enzymes activities in the blood serum caused by the effects of ghrelin should be regarded as the response of the lysosomal system. (nel.edu)
  • Lysosomal storage disorders include a heterogeneous group of approximately 70 different rare diseases marked by diverse genetic impairments causing the loss of specific enzymes and subsequent metabolite accumulation in the lysosomes. (rarediseaseadvisor.com)
  • Gene therapy is experimental but in the future may help correct both somatic and neurologic abnormalities in a lysosomal storage disorder. (medscape.com)
  • SDS-Page: Recombinant Human Lipase A Protein [H00003988-P01] - 12.5% SDS-PAGE Stained with Coomassie Blue. (novusbio.com)
  • Genes Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body or the code for functional ribonucleic. (msdmanuals.com)
  • In general, transplantation yields the best results when performed early in the course of the disease (ie, in an asymptomatic affected sibling of a child with a lysosomal storage disorder), in centers with experience in performing transplantations to treat inherited metabolic disorders, and in patients healthy enough to tolerate the conditioning and transplantation regimen. (medscape.com)
  • It develops medicines to treat conditions such as atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), hypophosphatasia (HPP), lysosomal acid lipase de?ciency (LAL-D), neurofibromatosis type 1 plexiform neurofibromas (NF1 PN), neuromyelitis optica spectrum disorder (NMOSD) and paroxysmal nocturnal hemoglobinuria (PNH). (pharmaceutical-technology.com)
  • Accumulated data indicate that hematopoietic stem cell transplantation may be effective under optimal conditions in preventing the progression of central nervous system symptoms in neuronopathic forms of lysosomal storage diseases (such as Krabbe disease), including some of the mucopolysaccharidoses, oligosaccharidoses, sphingolipidoses, and lipidoses as well as peroxisome disorders such as X-linked adrenoleukodystrophy. (medscape.com)
  • Accumulated data indicate that hematopoietic stem cell transplantation may be effective under optimal conditions in preventing the progression of central nervous system symptoms in neuronopathic forms of lysosomal storage diseases, including some of the mucopolysaccharidoses, oligosaccharidoses, sphingolipidoses, and lipidoses. (medscape.com)
  • Age of onset and clinical manifestations may vary widely among patients with a given lysosomal storage disease, and significant phenotypic heterogeneity between family members carrying identical mutations has been reported. (medscape.com)
  • In the blood serum the activity of cathepsins D and L, alanine aminopeptidase, acid phosphatase, lysosomal lipase and lysosomal esterase was determined. (nel.edu)
  • In the absence of this enzyme, called lysosomal acid lipase, fats accumulate in the body's cells and tissues, causing symptoms such as growth failure, enlarged liver, diarrhoea and malabsorption (when nutrients from food are not easily absorbed during digestion). (europa.eu)
  • 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 Hypercholesterolemia Market based on drug class can be further segmented into Statins, Niacin, Bile-Acid Resins, Fibric Acid Derivatives and Cholesterol Absorption Inhibitors. (industryarc.com)
  • The enzyme needed to break down cholesterol and triglycerides, called lysosomal acid lipase, does not work correctly. (msdmanuals.com)
  • Lysosomal storage diseases are generally classified by the accumulated substrate and include the sphingolipidoses, oligosaccharidoses, mucolipidoses, mucopolysaccharidoses (MPSs), lipoprotein storage disorders, lysosomal transport defects, neuronal ceroid lipofuscinoses and others. (medscape.com)
  • After the degradation of damaged proteins and lipids, amino acids and fatty acids are released into the cytoplasm and recycled for new biosynthesis of cellular components or energy production [ 4 ]. (hindawi.com)
  • Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. (bvsalud.org)
  • We identified a subset of lipotoxic monounsaturated fatty acids associated with decreased membrane fluidity. (bvsalud.org)
  • Differential diagnosis includes familial hypercholesterolemia, non-alcoholic fatty liver disease, cryptogenic cirrhosis, and combined hyperlipidemia, as well as other lysosomal storage disorders. (orpha.net)
  • Lysosomal storage diseases describe a heterogeneous group of dozens of rare inherited disorders characterized by the accumulation of undigested or partially digested macromolecules, which ultimately results in cellular dysfunction and clinical abnormalities. (medscape.com)
  • One of the most common lysosomal storage disorders is Gaucher disease, discussed below. (medscape.com)
  • Of the more than 50 known lysosomal storage diseases (LSDs)-rare inherited metabolic disorders-only seven can be treated with approved enzyme-replacement therapies. (news-medical.net)
  • Hypersensitivity reaction during enzyme replacement therapy in lysosomal storage disorders. (rarediseaseadvisor.com)
  • Immunostaining for lysosomal fat accumulation may facilitate diagnosis. (orpha.net)
  • Autophagy is a cellular catabolic process that eliminates damaged cell organelles, unfolded proteins, and various intracellular pathogens through lysosomal degradation. (hindawi.com)
  • It is an inborn error of metabolism that causes a lysosomal storage disease. (wikipedia.org)
  • 4-Methylumbelliferyl palmitate is used as a fluorogenic substrate for a subclass of esterases called lipase. (goldbio.com)
  • Our data suggest that ATGL releases arachidonic acid (AA) from LDs to serve as the substrate for PG synthesis. (bvsalud.org)
  • More than 50 lysosomal storage diseases have been described, some of which are discussed in this article. (medscape.com)
  • Thus far, ERT has been largely unsuccessful in improving central nervous system manifestations of the lysosomal storage diseases, putatively due to difficulty in penetrating the blood-brain barrier. (medscape.com)
  • This has led to active clinical trials evaluating the safety and efficacy of intrathecal enzyme delivery in several lysosomal storage diseases (see www.ClinicalTrials.gov ). (medscape.com)
  • The availability of both ERT and hematopoietic stem cell transplantation has prompted ongoing consideration of newborn screening efforts to diagnose lysosomal storage diseases. (medscape.com)
  • 4-Methylumbelliferyl palmitate has often been used as one of the lipase substrates in studies involving either of these diseases. (goldbio.com)
  • The work is based on the AI work of sister company DeepMind in predicting the structure of proteins directly from its amino acid sequence with atomic-level accuracy. (biospace.com)