Cholesteryl Ester Crystals in Lysosomal Acid Lipase Deficiency

Vt, Ivashkin; Zharkova, Maria

doi:10.1056/nejmicm1610060

Cited by 8 publications

(7 citation statements)

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“…Consistent with reduced acid CE hydrolase activity, we observed more neutral lipids by ORO staining ( Figure 3 D) and elevated CE concentrations in Lal-/- placentas, whereas TG levels remained unchanged ( Figure 3 E). In livers of adult Lal-/- mice [ 17 ] and LAL-deficient patients [ 24 ], the increased amount of neutral lipids (CE and TG) accumulates in lysosomes and can form CE crystals. These thin, crystalline structures were also visible in electron micrographs of Lal-/- placentas ( Figure 3 F, black arrows).…”

Section: Resultsmentioning

confidence: 99%

“…Using electron microscopy, we observed CE crystals in the placenta of Lal-/- mice. These crystals are known to be present in livers of adult Lal-/- mice [ 13 , 14 , 17 ] and LAL-deficient patients [ 24 ]. Although the presence of crystallized FC has been described in atherosclerotic lesions of humans and rabbits [ 30 , 31 , 32 , 33 ], the existence of FC crystals in Lal-/- mice is unlikely because FC concentrations in placentas and fetal livers were comparable to levels in WT tissues.…”

Section: Discussionmentioning

confidence: 99%

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Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth

Kuentzel

Akhmetshina

et al. 2021

IJMS

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Cholesterol and fatty acids are essential lipids that are critical for membrane biosynthesis and fetal organ development. Cholesteryl esters (CE) are degraded by hormone-sensitive lipase (HSL) in the cytosol and by lysosomal acid lipase (LAL) in the lysosome. Impaired LAL or HSL activity causes rare pathologies in humans, with HSL deficiency presenting less severe clinical manifestations. The infantile form of LAL deficiency, a lysosomal lipid storage disorder, leads to premature death. However, the importance of defective lysosomal CE degradation and its consequences during early life are incompletely understood. We therefore investigated how defective CE catabolism affects fetus and infant maturation using Lal and Hsl knockout (-/-) mouse models. This study demonstrates that defective lysosomal but not neutral lipolysis alters placental and fetal cholesterol homeostasis and exhibits an initial disease pathology already in utero as Lal-/- fetuses accumulate hepatic lysosomal lipids. Immediately after birth, LAL deficiency exacerbates with massive hepatic lysosomal lipid accumulation, which continues to worsen into young adulthood. Our data highlight the crucial role of LAL during early development, with the first weeks after birth being critical for aggravating LAL deficiency.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth

Kuentzel

Akhmetshina

et al. 2021

IJMS

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“…12 On the other hand, liver biopsy shows liver morphology findings that can be suggestive but not confirmatory, such as microvesicular steatosis with Kupffer cell involvement, fibrosis, micronodular cirrhosis, sea-blue histiocytosis and cholesterol ester crystals. 4,6,12,30,32,33 Other findings include lipid accumulation in reticuloendothelial cells of the spleen and vacuolated macrophages with lipids that infiltrate the lamina propria with gastrointestinal tissue architecture destruction and the consequent dysfunction of enterocytes absorbent and enzymatic activity. 6 In immunohistochemical testing, cathepsin D lysosomal markers, and lysosomal membrane-associated proteins 1 and 2 (LAMP1 and LAMP2) can be used.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Lysosomal acid lipase deficiency, a rare pathology

Gómez-Duarte¹,

García²,

Botero³

et al. 2023

GMM

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vessels, the spleen, adrenal glands, hematopoietic system, lymph nodes and gastrointestinal tract. In addition, it is associated with reduced generation of free cholesterol and free fatty acids. 1,[3][4][5][6][7][8][9][10] The decrease in free cholesterol translates into sterol regulatory elements and HMG-CoA increased activity, with a corresponding increase in free cholesterol and free fatty acids synthesis. 4,11 On the other hand, there is an

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“…12 Por otra parte, la biopsia hepática muestra hallazgos de la morfología hepática que pueden ser sugestivos más no confirmatorios, tales como esteatosis microvesicular con afectación de las células de Kupffer, fibrosis, cirrosis micronodular, histiocitosis en mar azul y cristales de esteres de colesterol. 4,6,12,30,32,33 Otros hallazgos son acumulación de lípidos en las células reticuloendoteliales del bazo y macrófagos vacuolados con lípidos que infiltran la lámina propia con destrucción de la arquitectura del tejido gastrointestinal y la consiguiente disfunción en la actividad absorbente y enzimática de los enterocitos. 6 En los exámenes de inmunohistoquímica se pueden usar marcadores lisosomales de catepsina D, proteínas 1 y 2 asociadas con la membrana lisosomal (LAMP1 y LAMP2).…”

Section: Diagnósticounclassified

Deficiencia de lipasa ácida lisosomal, una patología infrecuente

Gómez-Duarte

García

Botero

et al. 2019

GMM

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El déficit de lipasa ácida lisosomal es una enfermedad genética poco prevalente, con alta morbimortalidad en niños y adultos. Se caracteriza por alteración del metabolismo lipídico que genera depósitos de ésteres de colesterol y triglicéridos en el organismo. La presentación clínica depende de la actividad enzimática. Se debe sospechar en pacientes con alteraciones lipídicas o alteraciones hepáticas después de descartar otros diagnósticos. Actualmente existe la opción de utilizar enzima recombinante, la cual puede mejorar los parámetros lipídicos y hepáticos, así como detener la progresión de la enfermedad. Es imperioso realizar el diagnóstico oportuno para iniciar de forma temprana el tratamiento específico, con el fin de prevenir la morbimortalidad. Se llevó a cabo revisión de la literatura en torno del déficit de lipasa ácida lisosomal, para orientar acerca de su fisiopatología, manifestaciones clínicas, diagnóstico y tratamiento.

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Cholesteryl Ester Crystals in Lysosomal Acid Lipase Deficiency

Cited by 8 publications

References 0 publications

Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth

Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth

Lysosomal acid lipase deficiency, a rare pathology

Deficiencia de lipasa ácida lisosomal, una patología infrecuente

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