How is lecithin-cholesterol acyltransferase (LCAT) deficiency treated?

Updated: Oct 16, 2019
  • Author: Catherine Anastasopoulou, MD, PhD, FACE; Chief Editor: George T Griffing, MD  more...
  • Print


Currently, no definitive therapy for LCAT deficiency exists. When indicated, symptomatic treatment is indicated for anemia, renal insufficiency, and atherosclerosis. Renal replacement by dialysis is necessary in patients who develop kidney failure.

Research on recombinant human LCAT (rLCAT) in renal disease is ongoing. [7] Studies have shown evidence of lipid profile normalization after rLCAT injections in mice and increased HDL in humans with coronary artery disease. [8, 9]

In a phase 1 study, 16 stable patients with coronary artery disease were injected with a single intravenous adminstration of recombinant LCAT (ACP-501) replacement therapy. Six hours after injection, those who received higher doses of ACP-501 were found to have increased HDL-C levels compared to their baseline HDL-C levels. The increased HDL levels though lasted for only up to 4 days. The administration of ACP-501 was safe and well tolerated by these patients. [9]

In a study of rhLCAT infusions in FLD, a single patient with advanced renal disease was infused with rhLCAT (ACP-501) over 1 hour on 3 occasions in a dose optimization phase (0.3, 3.0, and 9.0 mg/kg), then 3.0 or 9.0 mg/kg every 1–2 weeks for 7 months in a maintenance phase. LCAT concentration peaked at the end of each infusion and decreased to near baseline over 7 days. Renal function generally stabilized or improved and anemia improved. After infusion, HDL-C rapidly increased, peaking near normal in 8–12 hours; LDL-C increased more slowly than HDL-C. The researchers noted that rhLCAT infusions were well tolerated and the positive findings support continued development of rhLCAT therapy. [10]

Freeman and colleagues conducted a study to investigate the mechanism for LCAT activation by compound A and to determine whether it can also increase activity of some natural LCAT mutations. Results of the study showed that compound A can activate a subset of FLD mutations by forming a hydrophobic adduct with Cys31 near the active site. Functional groups in compound A responsible for LCAT activation were also identified, and a new class of LCAT activators based on sulfhydryl-reactive beta-lactams were described. These findings provide insights into LCAT activation that may be used to design novel LCAT activators. [11]

Short-term whole blood or plasma transfusion has been tried to replace the LCAT enzyme in some patients with familial LCAT deficiency, but it did not correct anemia, proteinuria, or lipoprotein abnormalities.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!