LCAT Deficiency

Lecithin cholesterol acyltransferase (LCAT) is a protein important for cholesterol removal. In LCAT deficiency, a rare genetic disorder, this protein does not function correctly, resulting in harmful cholesterol accumulation.

1. Familial LCAT Deficiency: Characterized by complete loss of LCAT protein function.
2. Fish-Eye Disease: Characterized by partial loss of LCAT protein function.
   

LCAT Deficiency is identified by a combination of physical exam findings, lab tests, and genetic testing. The presence of cloudy deposits on the eyes and low levels of HDL (high-density lipoprotein, “good cholesterol”) should clue in providers and patients of LCAT Deficiency.

Familial LCAT Deficiency often presents before the age of 20. Genetic testing is helpful for the early detection of family members and future generations.

Patients with either form of LCAT deficiency have cloudy eyes due to scarring of the clear portion of the eye (cornea).

Those with Familial LCAT Deficiency have additional concerns including kidney problems with a risk of kidney failure by age 40 and anemia (low red blood cell count). Elevated cholesterol levels increase the risk of heart attacks and strokes in those with Fish-Eye disease.

Important lab tests include:

• Lipid panel
• Complete blood count
• Comprehensive metabolic panel

Patients may be advised to see specialists, including an eye doctor, lipid specialist, kidney doctor, and genetic counselor.

Patients with LCAT deficiency should maintain an active and healthy lifestyle. A heart-healthy diet that limits saturated fats is recommended to help maintain a healthy weight (within a normal BMI range of 18.5 – 24.9). Regular physical activity, aiming for 150 minutes per week is recommended, along with avoiding tobacco use and limiting alcohol consumption.

There is currently no cure for LCAT deficiency. Treatment focuses on medications that prevent long-term complications related to elevated cholesterol levels.

• Cholesterol Lowering Medications: Statins are used as a main-stay treatment to lower cholesterol levels.
• ACE-inhibitors and ARBs: These blood pressure medications (such as lisinopril, enalapril for ACE-inhibitors, and losartan, valsartan for ARBs) are used alongside statin therapy to protect the kidneys from damage.

Patients diagnosed with LCAT deficiency should see the following specialists:

• A lipid specialist
• An eye doctor (ophthalmologist)
• A kidney doctor (nephrologist)
• Patients can use the “Find a Clinician” resource offered by the NLA to identify lipid specialists in their area. Primary care providers can also refer patients to the specialists mentioned above.

1. Lecithin cholesterol acyl transferase) Natural History Study (LCAT NHS) (actively recruiting)
2. Summary: This study, conducted by the University of Pennsylvania is actively collecting data from patients with a known diagnosis of LCAT deficiency to improve understanding and assist doctors nationwide.
3. Analysis of Samples Collected From a Subject Who Received ACP- 501 (Human Recombinant Lecithin:Cholesterol Acyltransferase [rhLCAT]) (completed)
4. Summary: This clinical trial tested rhLCAT (human recombinant LCAT), a drug that replaces the missing protein in 16 patients with LCAT deficiency. This initial stage of investigation of the drug resulted in an increase in HDL (“good cholesterol”) with no serious harm to patients.
5. Further findings from the clinical trial can be found in the 2016 Publication (Shamburek, R, et. al).

University of Pennsylvania CureTalks: Understanding Lecithin Cholesterol Acyltransferase Deficiency Disorders

Description: This talk provides a summary of LCAT Deficiency and includes a first-hand account from patient advocate Jason S. Marshall

References

Althaf MM, Almana H, Abdelfadiel A, Amer SM, Al-Hussain TO. Familial lecithin-cholesterol acyltransferase (LCAT) deficiency; a differential of proteinuria. J Nephropathol. 2015;4(1):25-28. doi:10.12860/jnp.2015.05

Mehta R, Elías-López D, Martagón AJ, et al. LCAT deficiency: A systematic review with the clinical and genetic description of Mexican kindred. Lipids in Health and Disease. 2021;20(1). doi:10.1186/s12944-021-01498-6

Oldoni F, Baldassarre D, Castelnuovo S, et al. Complete and partial lecithin:cholesterol acyltransferase deficiency is differentially associated with atherosclerosis. Circulation. 2018;138(10):1000-1007. doi:10.1161/circulationaha.118.034706

Shamburek RD, Bakker-Arkema R, Shamburek AM, et al. Safety and Tolerability of ACP-501, a recombinant human lecithin:cholesterol acyltransferase, in a phase 1 single-dose escalation study. Circulation Research. 2016;118(1):73-82. doi:10.1161/circresaha.115.306223

Shamburek RD, Bakker-Arkema R, Shamburek AM, et al. Safety and Tolerability of ACP-501, a recombinant human lecithin:cholesterol acyltransferase, in a phase 1 single-dose escalation study. Circulation Research. 2016;118(1):73-82. doi:10.1161/circresaha.115.306223

Vitali C, Bajaj A, Nguyen C, et al. A systematic review of the natural history and biomarkers of primary lecithin:cholesterol acyltransferase deficiency. Journal of Lipid Research. 2022;63(3):100169. doi:10.1016/j.jlr.2022.100169

Yang K, Wang J, Xiang H, Ding P, Wu T, Ji G. LCAT- targeted therapies: Progress, failures and future. Biomedicine & Pharmacotherapy. 2022;147:112677. doi:10.1016/j.biopha.2022.112677