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LAL deficiency

Hanrui Zhang
PURPOSE OF REVIEW: Lysosomal acid lipase (LAL), encoded by the LIPA gene, is an essential lysosomal enzyme that hydrolyzes cholesteryl ester and triglyceride delivered to the lysosome. This review highlights the novel pathophysiological role of LAL, the functional genomic discoveries of LIPA as a risk locus for coronary heart diseases (CHD), and the clinical advance in therapies for LAL deficiency. RECENT FINDINGS: The essential role of LAL in lipid metabolism has been confirmed in human and mice with LAL deficiency...
March 15, 2018: Current Opinion in Lipidology
Elmar Aigner, Alexandra Feldman, Daniel Neureiter, Christian Datz, Vlad Ratziu, Bernhard Paulweber
No abstract text is available yet for this article.
March 2018: American Journal of Gastroenterology
Marco Antonio Curiati, Sandra Obikawa Kyosen, Vanessa Gonçalves Pereira, Francy Reis da Silva Patrício, Ana Maria Martins
Lysosomal acid lipase (LAL) deficiency is an autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene that leads to premature organ damage and mortality. We present retrospective data from medical records of 5 Brazilian patients, showing the broad clinical spectrum of the disease.
2018: Case Reports in Pediatrics
Bikrant Bihari Lal, Seema Alam, Rajeev Khanna, Dinesh Rawat
There are no evidence-based recommendations on the ideal dose and regimen for supplementation of vitamin D in children with chronic liver disease (CLD). This study aimed to compare the safety and efficacy of weekly and stoss regimens for treatment of vitamin D deficiency in these children. Children between the ages of 1 to 18 years with CLD and hypovitaminosis D defined by 25-OH vitamin D (25(OH)D) < 30µg/l were included. They were randomized to receive either stoss regimen (600,000 IU on day 1) or weekly (60,000 IU weekly) regimen of vitamin D...
March 4, 2018: European Journal of Pediatrics
Laura López de Frutos, Jorge J Cebolla, Pilar Irún, Ralf Köhler, Pilar Giraldo
BACKGROUND: Erythrocyte volume regulation and membrane elasticity are essential for adaptation to osmotic and mechanical stress, and life span. Here, we evaluated whether defective cholesterol trafficking caused by the rare lysosomal storages diseases (LSDs), Niemann-Pick type C (NPC) and Lysosomal acid lipase (LAL) deficiency (LALD) impairs these properties. Moreover, we tested whether measurements of cholesterol membrane content and osmotic resistance serve as a screening test for these LSDs...
February 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Julian F Guest, Andy Ingram, Nadia Ayoub, Christian J Hendriksz, Elaine Murphy, Yusof Rahman, Patrick McKiernan, Helen Mundy, Patrick Deegan
OBJECTIVE: To estimate clinical progression and resource utilisation together with the associated costs of managing children and adults with LAL Deficiency, at a tertiary referral centre in the UK. METHODS: A retrospective chart review was undertaken of patients in the UK with a confirmed diagnosis of LAL Deficiency who were managed at a LAL Deficiency tertiary referral treatment centre. Patients' pathways, treatment patterns, health outcomes and resource use were quantified over differing lengths of time for each patient enabling the NHS cost of patient management in tertiary care to be estimated...
2018: PloS One
Madalina Duta-Mare, Vinay Sachdev, Christina Leopold, Dagmar Kolb, Nemanja Vujic, Melanie Korbelius, Dina C Hofer, Wenmin Xia, Katharina Huber, Martina Auer, Benjamin Gottschalk, Christoph Magnes, Wolfgang F Graier, Andreas Prokesch, Branislav Radovic, Juliane G Bogner-Strauss, Dagmar Kratky
Lysosomal acid lipase (LAL) is the only known enzyme, which hydrolyzes cholesteryl esters and triacylglycerols in lysosomes of multiple cells and tissues. Here, we explored the role of LAL in brown adipose tissue (BAT). LAL-deficient (Lal-/-) mice exhibit markedly reduced UCP1 expression in BAT, modified BAT morphology with accumulation of lysosomes, and mitochondrial dysfunction, consequently leading to regular hypothermic events in mice kept at room temperature. Cold exposure resulted in reduced lipid uptake into BAT, thereby aggravating dyslipidemia and causing life threatening hypothermia in Lal-/- mice...
January 24, 2018: Biochimica et Biophysica Acta
Thomas Grenkowitz, Nikolaus Buchmann, Tim Hollstein, Ilja Demuth, Elisabeth Steinhagen-Thiessen, Ursula Kassner
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Euridiki Drogari, George Pappas, Eleftherios Iliadis, Nina Manolaki
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Enrique Rodríguez-García, Miriam Gil-Serret, María Concepción García-Jiménez, María Luisa González-Diéguez, Pablo Del Valle Loarte, Miguel Angel Barba-Romero, David Gil-Ortega, Rosa Bernal-López, Nuria Amigó, Raquel Yahyaoui
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Timothy M Reynolds, Clare Mewies, John Hamilton, Anthony S Wierzbicki
AIMS: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder of cholesterol ester storage associated with hepatic disease, cirrhosis and accelerated atherosclerosis. Its prevalence in the general population, patients with dyslipidaemia and raised transaminases is unclear. This study attempted to identify the prevalence of LALD from patients with abnormal results in laboratory databases. METHODS: Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of low high-density lipoprotein-cholesterol (≤0...
January 22, 2018: Journal of Clinical Pathology
Sophia Masi, Naveen Chennamaneni, Frantisek Turecek, C Ronald Scott, Michael H Gelb
BACKGROUND: Deficiency of lysosomal acid lipase (LAL) causes Wolman disease and cholesterol ester storage disease. With the recent introduction of enzyme replacement therapy to manage LAL deficiency comes the need for a reliable assay of LAL enzymatic activity that can be applied to dried blood spots (DBS). METHODS: We prepared and tested a library of analogs of palmitoyl 4-methylumbelifferyl esters to find a highly active and specific substrate for LAL in DBS. The LAL assay was optimized leading to both LC-MS/MS and fluorometric assay of LAL...
January 16, 2018: Clinical Chemistry
Ornella Guardamagna, Federica Guaraldi
LAL-deficiency (LAL-D) is a rare and systemic condition, secondary to LIPA gene mutations, responsible for lysosomal accumulation of cholesteryl esters and triglycerides, whose manifestations are very heterogeneous in terms of age of onset, severity and type of clinical and radiological manifestations. Dyslipidemia, hepatomegaly and hepatosteatosis with increased levels of transaminases are the most common features. The increased risk of premature atherosclerosis and cardiovascular disorders,, secondary to a generalized alteration of lipid profile and lipoprotein dysfunction associated with LAL-D, has been increasingly pointed out...
January 11, 2018: Current Pediatric Reviews
Ashok Kumar Yadav, Vivek Kumar, Debasish Banerjee, Krishan Lal Gupta, Vivekanand Jha
Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤ 20 ng/ml [CTRI/2013/05/003648]...
January 10, 2018: Journal of Steroid Biochemistry and Molecular Biology
Kwang Yeon Kim, Ju Whi Kim, Kyung Jae Lee, Eunhyang Park, Gyeong Hoon Kang, Young Hun Choi, Woo Sun Kim, Jung Min Ko, Jin Soo Moon, Jae Sung Ko
Patients with lysosomal acid lipase (LAL) deficiency and glycogen storage disease (GSD) demonstrated hepatomegaly and dyslipidemia. In our case, a 6-year-old boy presented with hepatosplenomegaly. At 3 years of age, GSD had been diagnosed by liver biopsy at another hospital. He showed elevated serum liver enzymes and dyslipidemia. Liver biopsy revealed diffuse microvesicular fatty changes in hepatocytes, septal fibrosis and foamy macrophages. Ultrastructural examination demonstrated numerous lysosomes that contained lipid material and intracytoplasmic cholesterol clefts...
December 2017: Pediatric Gastroenterology, Hepatology & Nutrition
R Vázquez-Frias, J E García-Ortiz, P F Valencia-Mayoral, G E Castro-Narro, P G Medina-Bravo, Y Santillán-Hernández, J Flores-Calderón, R Mehta, C A Arellano-Valdés, L Carbajal-Rodríguez, J I Navarrete-Martínez, M L Urbán-Reyes, M T Valadez-Reyes, F Zárate-Mondragón, A Consuelo-Sánchez
INTRODUCTION: Lysosomal acid lipase deficiency (LAL-D) causes progressive cholesteryl ester and triglyceride accumulation in the lysosomes of hepatocytes and monocyte-macrophage system cells, resulting in a systemic disease with various manifestations that may go unnoticed. It is indispensable to recognize the deficiency, which can present in patients at any age, so that specific treatment can be given. The aim of the present review was to offer a guide for physicians in understanding the fundamental diagnostic aspects of LAL-D, to successfully aid in its identification...
January 2018: Revista de Gastroenterología de México
Adam M Lopez, Jen-Chieh Chuang, Stephen D Turley
Although only a small proportion of cholesterol in the body is esterified, in several diseases marked expansion of the esterified cholesterol (EC) pool occurs. These include Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD) which both result from mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). The respective contributions that our three cholesterol esterifying enzymes make to EC production, especially in disorders like CESD, are not well defined. The current studies represent a detailed exploration of our earlier findings in young male LAL-deficient mice also missing sterol-O-acyltransferase 2 (SOAT2, also called ACAT2)...
December 12, 2017: Steroids
S Synoracki, S Kathemann, K W Schmid, H Jastrow, H A Baba
BACKGROUND AND CLINICAL SETTING: Lysosomal acid lipase deficiency is an autosomal recessive storage disease caused by mutations in the LIPA gene. The accumulation of cholesteryl esters and triglycerides in hepatocytes lead to hepatomegaly with progressive fibrosis and liver cirrhosis. Characteristically, patients have a hepatomegaly combined with high serum levels of cholesterol, LDL-cholesterol and in some cases triglyceride, whereas HDL-cholesterol is decreased. Histologically, hepatocytes show a microvesicular steatosis with typically ballooned Kupffer cells...
December 12, 2017: Der Pathologe
Swetha Parvathaneni, Xing Lu, Ritu Chaudhary, Ashish Lal, Srinivasan Madhusudan, Sudha Sharma
Sensitivity of cancer cells to DNA damaging chemotherapeutics is determined by DNA repair processes. Consequently, cancer cells may upregulate the expression of certain DNA repair genes as a mechanism to promote chemoresistance. Here, we report that RECQ1, a breast cancer susceptibility gene that encodes the most abundant RecQ helicase in humans, is a p53-regulated gene, potentially acting as a defense against DNA damaging agents. We show that RECQ1 mRNA and protein levels are upregulated upon treatment of cancer cells with a variety of DNA damaging agents including the DNA-alkylating agent methylmethanesulfonate (MMS)...
September 29, 2017: Oncotarget
Ashok Kumar Yadav, Vivek Kumar, Vinod Kumar, Debasish Banerjee, Krishan Lal Gupta, Vivekanand Jha
Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo-controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3-G4 and vitamin D ≤20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648)...
October 17, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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