Lecithin-Cholesterol Acyl Transferase Deficiency



Lecithin-Cholesterol Acyl Transferase Deficiency


Ami Bhalodia, MD





Key Facts


Terminology



  • Complete or partial LCAT deficiency


  • Familial LCAT deficiency


  • Fish eye disease


Etiology/Pathogenesis



  • Defect in LCAT-mediated cholesterol ester-formation


  • Mutation of LCAT gene on chromosome 16q22


Clinical Issues



  • Corneal opacities and cataracts


  • Hemolytic anemia


  • Renal insufficiency with proteinuria


  • Atherosclerosis in rare cases


Microscopic Pathology



  • Glomerular mesangial expansion



    • Bubbly, vacuolated matrix


  • Capillary loop thickening



    • GBM “spikes,” vacuoles, duplication


  • Tubular atrophy and interstitial fibrosis



    • Interstitial foam cells


  • EM: Rounded granular and lamellar dense lipid deposits in GBM and mesangium


  • Lipid deposits in liver, spleen, and bone marrow


Ancillary Tests



  • Laboratory tests



    • Reduced plasma total cholesterol


    • Decreased high-density lipoprotein


Top Differential Diagnoses



  • Hepatic glomerulopathy


  • Alagille syndrome







Lipids deposited in LCAT deficiency are extracted by solvents employed in tissue processing. This results in a vacuolated appearance to the mesangial matrix image and capillary loop basement membranes.






This electron micrograph shows the characteristic lipid deposits with a vacuolar appearance within the mesangial matrix. The accumulated material imparts a “honeycomb” appearance to the mesangium.


TERMINOLOGY


Abbreviations



  • Lecithin-cholesterol acyltransferase (LCAT) deficiency


Synonyms



  • Phosphatidylcholine-sterol o-acyltransferase deficiency


Definitions



  • Diseases caused by complete or partial LCAT deficiency



    • Familial LCAT deficiency (FLD)


    • Fish eye disease (FED)


ETIOLOGY/PATHOGENESIS


Genetic Disorder



  • Autosomal recessive


  • Mutation of LCAT gene on chromosome 16q22



    • More than 36 mutations described


  • Defect in LCAT-mediated cholesterol ester formation


  • Failure to secrete active LCAT into plasma



    • Accumulation of unesterified cholesterol in cornea, kidneys, and erythrocytes


  • LCAT normally carried in high-density lipoproteins (HDL) with ApoA1



    • Decreased HDL


  • Increased free cholesterol-phospholipid vesicles (LpX)


Animal Model



  • Murine LCAT deficiency (increased LpX)


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare cases reported worldwide



      • 60 with complete LCAT deficiency


      • 20 with partial LCAT deficiency


  • Ethnicity



    • Initially reported in Norway



      • Now appears widely distributed


Presentation



  • Complete LCAT deficiency



    • Familial LCAT deficiency


    • Corneal cataracts


    • Hemolytic anemia


    • Renal insufficiency by 4th decade



      • Proteinuria may begin in childhood


      • Progression of renal disease is variable


    • Atherosclerosis in rare cases


    • Hypertension


  • Partial LCAT deficiency



    • Fish eye disease


    • Corneal opacities



      • Resemble eyes of a boiled fish


    • No overt renal disease


Laboratory Tests



  • Reduced plasma total cholesterol


  • Decreased HDL


  • Low LCAT activity in plasma


  • Urinalysis shows hematuria, leukocyturia, and casts


Treatment



  • Medical treatment for anemia, renal insufficiency, and atherosclerosis


  • Renal failure



    • Dialysis


    • Renal transplantation


  • Corneal transplantation


Prognosis



  • Renal transplantation



    • Moderately successful


    • Does not reverse serum lipoprotein abnormalities


    • Mesangial lipid deposits recur within weeks



      • Do not initially impair renal function



MICROSCOPIC PATHOLOGY


Histologic Features

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lecithin-Cholesterol Acyl Transferase Deficiency

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