We have shown that ether-linked glycerolipids accumulated in the adrenal, liver, and spleen of a male Chinese infant with Wolman's disease; the increases were mainly in the alkyl and alk-1-enyl glycerolipids that did not contain phosphorus. Alkyldiacylglycerol accounted for a portion of the rise in the neutral alkylglycerols. The spleen also contained increased amounts of ether-linked phosphoglycerides of the alkyl and alk-1-enyl types. Organs from a Niemann-Pick patient were also included in this study; they did not show comparable rises in the content of ether-linked glycerolipids, suggesting the possibility that storage of these compounds may be characteristic of Wolman's disease, or a variant form thereof.
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Nutrients
December 2024
Pediatric Hepatology and Liver Transplant Unit, Department of Pediatrics, ERN Rare Liver ERN TransplantChild, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease with two distinct phenotypes, an infantile-onset form (formerly Wolman disease) and a later-onset form (formerly cholesteryl ester storage disease). The objective of this narrative review is to examine the most important aspects of the diagnosis and treatment of LAL-D and to provide practical expert recommendations. The infantile-onset form occurs in the first weeks of life and is characterized by malnourishment and failure to thrive due to gastrointestinal impairment (vomiting, diarrhea, malabsorption), as well as systemic inflammation, hepatosplenomegaly, and adrenal calcifications.
View Article and Find Full Text PDFCureus
November 2024
Pediatrics, "Carol Davila" University of Medicine and Pharmacy, Bucharest, ROU.
Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive genetic disease arising from mutations in the lipase A, lysosomal acid type (LIPA) gene, characterised by the formation of cholesterol esters and triglyceride storages, primarily in the liver and spleen. By analysing the level of lysosomal acid lipase (LAL), two forms were described in the literature: Wolman disease and cholesteryl-ester storage disease (CESD). Wolman disease usually manifests with rapidly progressive symptoms within the first year of life, while CESD is a latent condition, with significant features appearing later in life.
View Article and Find Full Text PDFMol Ther
December 2024
Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43215, USA; Department of Pediatrics, The Ohio State University School of Medicine, Columbus, OH 43210, USA. Electronic address:
Lysosomal acid lipase deficiency (LAL-D) is caused by mutations in the LIPA gene, which encodes the lysosomal enzyme that hydrolyzes triglycerides and cholesteryl esters to free fatty acids and free cholesterol. The objective of this study was to develop a curative single-treatment therapy for LAL-D using adeno-associated virus (AAV). Treatment at both early (1-2 days) and late (8-week) timepoints with rscAAVrh74.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.
Lysosomal acid lipase (LAL) is the only known enzyme that degrades cholesteryl esters and triglycerides at an acidic pH. In LAL deficiency (LAL-D), dysregulated expression of matrix metalloproteinase 12 (MMP-12) has been described. The overexpression of MMP-12 in myeloid lineage cells causes an immune cell dysfunction resembling that of knockout ( KO) mice.
View Article and Find Full Text PDFFetal Diagn Ther
October 2024
Division of Ultrasound in ObGyn at Lis Maternity and Women's Hospital, Tel Aviv Medical Center, Tel Aviv, Israel.
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