LCAT Deficiency Disorders: natural history and identification of biomarkers

Brief description of study

Familial lecithin:cholesterol acyl transferase (LCAT) deficiency (FLD) is a rare, hereditary disease with no treatment. It is caused by mutations in the gene for LCAT, an enzyme that is made in the liver and plays a role in the body’s ability to process (“metabolize”) cholesterol. People with FLD have very low to undetectable levels of the LCAT enzyme and very low HDL cholesterol levels. People with FLD typically present with clouding of the clear front surface of the eyes (“corneal opacity”), a shortage of red blood cells (“anemia”) and lose protein into their urine (“proteinuria”). People with FLD often develop renal failure by their 40’s and require hemodialysis or a kidney transplant. Mutations in the LCAT gene are also the cause of fish eye disease (FED). Similar to FLD, FED is characterized by very low HDL cholesterol levels as well as by corneal opacity. However, people with FED are usually not ask sick and generally do not develop renal failure.

LCAT deficiency, including FLD and FED, is extremely rare. Our current understanding of these diseases is based on just a few published case reports or small studies. We still lack an understanding of how LCAT mutations affect people and what are the different disease outcomes that result from these mutations.

The purpose of the LCAT Natural History Study (LCAT NHS) is to help identify people with a mutation in the gene for LCAT, collect and store information about their medical history and disease course, and to assess for associations and follow changes in clinical features and biomarkers of disease over a four-year period. This information will help health care providers better understand the natural history of disease of LCAT deficiency, specifically the different patterns of disease and disease progression. It will also help researchers identify biomarkers (clinical or laboratory measurements) that will help healthcare providers identify which patients are at higher risk for adverse disease outcomes, like renal disease. These biomarkers may also help evaluate the effectiveness of future treatments in clinical trials.

Detailed description of study

Study staff will collect information from previous clinical visits such as lab tests, physical exam findings, renal and cardiovascular imaging, findings from kidney biopsies and eye exams, and medication and other treatments. As part of this study we are asking your permission to reach out to your doctors to obtain medical records and stored samples (such as serum or plasma or biopsies) from past visits.

You may also be asked to join a web-based patient portal to complete a patient-outcomes survey.

If you participate in this study, you will also be asked to do the following things at different times:

o Answer questions about your:

o Demographic information (year of birth, age, gender, race/ethnicity, country)

o LCAT deficiency diagnosis such as year of diagnosis, type of diagnosis (clinical, genetic), genotype information/LCAT mutation status

o Medical history and family history and any updates

o A review of your medications

If you are able to come to a study visit in person the following may happen:

o Physical examination including vital signs (height, weight, blood pressure, and heart rate)

o Urine and blood samples for laboratory testing. You will be required to fast for 10 hours before the blood tests. A small blood sample may also be taken 2-4 hours after a meal.

o The following will be tested: the different types of cholesterol and other fats in your blood (lipids), standard hematology (type and number of blood cells), blood chemistries such as sodium, potassium, and calcium, thyroid function, liver panel (function of the liver), kidney function and the level of protein in your urine

o Blood and urine samples may also be stored for future testing

o Genetic material will be collected

o Blood cells may be stored for future research

o You will have approximately 4.5 tablespoons of blood drawn annually.

o If not done previously, you will complete an eye exam.

o You may be seen by a doctor specialized in renal disease

Eligibility of study

You may be eligible for this study if you meet the following criteria:

Conditions:
LCAT Natural History Study
Age: Between 1 Years - 99 Years
Gender: All

Inclusion Criteria:

1. Males or Females, aged 1 year and older

2. Subjects with:

a. a diagnosis of primary LCAT deficiency based on investigator assessment or laboratory results AND/OR

b. a genetically confirmed mutation in the LCAT gene who are homozygous or compound heterozygous for LCAT loss-of-function mutations

3. Subjects or their legal guardian must be able to comprehend and be willing to provide a signed institutional review board/ethics committee (IRB/EC) approved Informed Consent Form

Exclusion Criteria:

1. Secondary causes of LCAT deficiency

2. Any other medical or psychological conditions that, in the opinion of the investigator, would compromise the subject’s safety or successful participation in the study, or confound the study data

Updated on 09 Mar 2024. Study ID: 833871

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