Identification and metabolic profiling of patients with lysosomal acid lipase deficiency

Journal of Clinical Lipidology
Clive R PullingerJohn P Kane

Abstract

Lysosomal acid lipase (LAL), encoded by the LIPA gene, catalyzes the intracellular hydrolysis of cholesteryl esters and triglycerides in hepatocytes and macrophages. LIPA defects cause accumulation of these lipids in lysosomes. LAL deficiency (LAL D) presents and progresses as a continuum with dyslipidemia, hepatomegaly, and liver fibrosis. To improve the understanding of the genetic basis of LAL D, an underappreciated cause of dyslipidemia and cirrhosis, we studied DNA samples from patients with various phenotypes of dyslipidemia. Participants (N = 1357) were identified by lipid profiles and screened for the common disease causing LIPA exon 8 skipping splice-site mutation (c.894G>A; p.Ser275_Gln298del; rs116928232). Six patients were heterozygous for this variant. Complete LIPA sequencing revealed a patient, subsequently confirmed to have LAL D, with a heterozygous frameshift mutation involving deletion of exon 4 (p.Gly77Valfs*17 c.230-106_c.428+541del). A family study revealed a sister with the same genotype and phenotype. Genetic, clinical, and lipoprotein profiles of these sisters plus 6 additional family members are reported. Profiles of 2 other LAL D patients monitored for 2 decades are presented. Cholesterol homeostasis ...Continue Reading

References

Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·R A AndersonG N Sando
Jan 1, 1995·Journal of Inherited Metabolic Disease·C L MaslenD R Illingworth
Feb 4, 2003·Journal of Lipid Research·Nirupa R MatthanAlice H Lichtenstein
Sep 1, 1955·The Journal of Clinical Investigation·R J HAVELJ H BRAGDON
Mar 1, 1956·A.M.A. Journal of Diseases of Children·A ABRAMOVM WOLMAN
Sep 9, 2008·Clinica Chimica Acta; International Journal of Clinical Chemistry·Amanda J HooperJohn R Burnett
Mar 25, 2009·Molecular Genetics and Metabolism·Livia PisciottaStefano Bertolini
Jul 16, 2011·The American Journal of Cardiology·Lin T GueyMary J Malloy
Apr 10, 2012·Clinica Chimica Acta; International Journal of Clinical Chemistry·John HamiltonPeter Galloway
Jan 26, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Manisha BalwaniAnthony G Quinn
Feb 21, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Stuart A ScottRobert J Desnick
Oct 15, 2013·Zeitschrift für Gastroenterologie·F FreudenbergS Koletzko

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Citations

Feb 6, 2019·Current Opinion in Lipidology·Ernst J SchaeferGregory Endress
Oct 17, 2019·Molecular Genetics & Genomic Medicine·Karen H Y WongClive R Pullinger
Dec 5, 2019·Biomolecules·Svetlana MikhailovaElena Shakhtshneider
Aug 15, 2017·Therapeutic Advances in Gastroenterology·Angelika L Erwin
Dec 12, 2020·Journal of Clinical Lipidology·Praneet K GillRobert A Hegele

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