China
Africa
Explore chapters and articles related to this topic
Lysosomal acid lipase deficiency: Wolman disease/cholesteryl ester storage disease
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
In the first patient with Wolman disease in whom mutations were identified, L179P was in compound with a frameshift mutation at nucleotide 634 (insT) causing a premature stop (Fs178) [4]. A majority of patients with Wolman disease have been homozygotes, and many had truncating mutations [8, 63, 64]. The common exon 8 splice site mutation at-1 was found to yield 3 percent of correctly spliced mRNA and a full-length enzyme [8]. On the other hand, sibs with Wolman disease homozygous for a splice site mutation at the same donor site had no correctly spliced mRNA and no enzyme activity.
Biochemical Aspects of Fatty Liver
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
It has been stated earlier that small fat droplets tend to fuse and that a unique large drop is the final result of fusion. There is, however, an exception to this. It is represented by Wolman disease, an inborn lysosomal disease characterized by the congenital lack of acid lipase. In this case, TG accumulate inside lysosomes and fusion does not occur, the cell acquiring the aspect of a foamy cell with the nucleus occupying a central position.
Metabolic Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephanie Grünewald, Alex Broomfield, Callum Wilson
Wolman disease is the term for the most severe clinical variant of acid lipase deficiency. Patients are symptomatic at birth and develop progressive feeding intolerance, diarrhoea, massive hepatosplenomegaly, liver cirrhosis and pulmonary infiltrates/inflammation secondary to lipid deposition. Death usually occurs during infancy. Patients frequently have enlarged adrenal glands with calcifications. The less severe phenotype, which often presents much later in childhood, is known as cholesterol ester disease.
Recommendations for overcoming challenges in the diagnosis of lysosomal acid lipase deficiency
Published in Expert Opinion on Orphan Drugs, 2022
Pilar Giraldo, Laura López de Frutos, Jorge J Cebolla
Lysosomal acid lipase deficiency (LALD; MIM#278000) is also known as acid cholesterol ester hydrolase deficiency. It is an ultrarare lysosomal storage disease (LSD) with a wide range of phenotypic variability and age of onset. Classically, the onset of the severe phenotype called Wolman disease (WD) is in the first days of life, and it can cause death in the first 12 months of life if it is not treated. On the other hand, the mild phenotype, also called cholesteryl ester storage disease (CESD), can arise from infancy to the fifth and sixth decade of life, with cardiovascular disease in the absence of liver failure being the main cause of death [1]. The estimated incidence of WD is 1 in 500,000 live births, and this is possibly higher for CESD, which tends to go more unnoticed. Using the prevalence of the most frequent genetic variant in CESD (NM_000235.3:c.894 G >A), the prevalence of CESD in the Caucasian and Hispanic populations has been estimated to be about ~0.8 per 100,000 (~1 in 130,000; 95% CI: ~1 in 90,000 to 1 in 170,000) [2].
Genetic background of coronary artery disease: clinical implications and perspectives
Published in Expert Review of Precision Medicine and Drug Development, 2020
Massimiliano Camilli, Giulia Iannaccone, Marco G. Del Buono, Filippo Crea, Nadia Aspromonte
LIPA, located at 10q23.31, encodes an enzyme called lysosomal acid lipase (LAL), which catalyzes the hydrolysis of cholesteryl esters and triglycerides in the lysosomes. LIPA has been recently identified as a locus related to CAD, inducing endothelial dysfunction [19–21]. Before GWAS in CAD, loss of function (LOF) mutations in LIPA were identified as causes of rare lysosomal disorders, such as Wolman disease and Cholesteryl esther storage disease (CESD). Although recombinant human LAL enzyme replacement therapy is likely to exert protective effects against premature atherosclerosis in CESD patients, it is unclear what the effects of recombinant human LAL treatment would be in CAD patients without LAL deficiency, as the role of LIPA in atherosclerosis mechanisms remains largely unclear [22].
Enzyme therapy: a forerunner in catalyzing a healthy society?
Published in Expert Opinion on Biological Therapy, 2020
Saptashwa Datta, K Narayanan Rajnish, C George Priya Doss, S. Melvin Samuel, E. Selvarajan, Hatem Zayed
Enzyme replacement therapy was the first publicized use of enzymes for therapeutic purposes. The possibility of using enzymes for the therapy of lysosomal storage diseases was proposed in 1964 by Dr. Christian de Duve [3]. Since its provenance, enzyme replacement therapy has made large strides and is currently used for the treatment of multiple enzyme deficiency disorders, including Gaucher disease [4], Fabry disease [5], Pompe disease [6], Hunter syndrome [7], Hurler–Scheie syndrome [8], Sly syndrome [9], Morquio A syndrome [10], Tay–Sachs disease [11], Wolman disease [12], adenosine deaminase-severe combined immune deficiency [13], hypophosphatasia [14], metachromatic leukodystrophy [15], Sphingomyelinase deficiency [16], homocystinuria [17], Maroteaux–Lamy syndrome [18], alpha-mannosidosis [19] and ceroid lipofuscinosis type 2 [20]. Pancreatic enzyme replacement therapy is a specialized category of replacement therapy using enzymes used for the therapy of exocrine pancreatic insufficiency, which can occur in various diseases, such as cystic fibrosis, chronic pancreatitis, and celiac disease [21]. Moreover, in the modern era, the therapeutic use of enzymes has been further applied for cancer treatment [22], wound healing [23], improving the life of patients suffering from irritable bowel syndrome [24], fighting antibiotic-resistant microbial infections [25] and gene therapy [26]. In this article, we review the properties of various enzymes, along with their efficacy in the treatment of various disorders. The enzymes have been grouped into sections based on the various diseases they are used to treat. This article also provides an update on recent developments in enzyme research and their application as therapeutics.