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Disease Profile

Familial LCAT deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

All ages

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ICD-10

E78.6

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

FLD; Norum disease; Complete LCAT deficiency

Categories

Blood Diseases; Congenital and Genetic Diseases; Endocrine Diseases;

Summary

Familial LCAT deficiency is a genetic disorder that affects the body's ability to process (metabolize) cholesterol. It is characterized by cloudiness of the clear front surface of the eye (corneal opacities), a shortage of red blood cells (hemolytic anemia), and kidney failure. Symptoms usually appear in adulthood and may also include enlargement of the liver (hepatomegaly), spleen (splenomegaly), and lymph nodes (lymphadenopathy), as well as an accumulation of fat in the artery walls (atherosclerosis).[1][2][3]
Familial LCAT deficiency is one of two types of LCAT deficiency; the other type of LCAT deficiency is fish-eye disease. Both types of LCAT deficiency are caused by mutations in the LCAT gene and are inherited in an autosomal recessive manner.[1][4] Although there is no specific treatment or cure for familial LCAT deficiency, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options for each person.

Symptoms

The signs and symptoms of familial LCAT deficiency are thought to be caused by a buildup of cholesterol in different areas of the body. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals.

The earliest symptom of familial LCAT deficiency, typically occurring in childhood, is cloudiness in the front surface of the eye (cornea), known as corneal opacities. Kidney disease, sometimes leading to kidney failure, usually begins in adolescence or early adulthood.[1][3] Other symptoms often found in individuals with LCAT deficiency include:[1][3]

  • Hemolytic anemia (shortage of red blood cells)
  • Enlargement of the liver (hepatomegaly), spleen (splenomegaly), or lymph nodes (lymphadenopathy)
  • Accumulation of fatty deposits in the artery walls (atherosclerosis)
  • Swelling of the optic nerve (papilledema)
  • A buildup of fat under the surface of the skin (xanthelasma)
  • Symptoms of kidney failure, such as high blood pressure

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Decreased HDL cholesterol concentration
Decreased circulating high-density lipoprotein cholesterol
Decreased HDL cholesterol
Low HDL-cholesterol

[ more ]

0003233
Foam cells
0003651
Hemolytic anemia
0001878
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Normochromic anemia
0001895
Opacification of the corneal stroma
0007759
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083

Cause

Familial LCAT deficiency is a genetic disorder caused by mutations in the LCAT gene. The LCAT gene provides instructions for making an enzyme (protein) called lecithin-cholesterol acyltransferase (LCAT). This enzyme is involved in removing cholesterol from the blood and tissues by helping it attach to a group of proteins, called lipoproteins. The cholesterol is then transported to the liver and sent to other tissues in the body or removed from the body.

The LCAT enzyme has two major functions: alpha and beta LCAT activity. Alpha-LCAT activity helps attach cholesterol to a lipoprotein called high-density lipoprotein (HDL), while beta-LCAT activity helps attach cholesterol to other lipoproteins called low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL).[1][3]

In familial LCAT deficiency, LCAT gene mutations either prevent the production of the LCAT enzyme or impair both the alpha-LCAT and beta-LCAT activity, reducing the enzyme's ability to attach cholesterol to lipoproteins. This is known as a complete LCAT deficiency. This likely leads to a buildup (deposit) of cholesterol in tissues throughout the body, including the corneas and kidneys.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    Although there is no cure for familial LCAT deficiency, there are ways to manage the signs and symptoms including:[3][5]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference contains information on Familial LCAT deficiency. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Familial LCAT deficiency. Click on the link to view a sample search on this topic.

          References

          1. complete LCAT deficiency. Genetics Home Reference (GHR). August 2013; https://ghr.nlm.nih.gov/condition/complete-lcat-deficiency.
          2. Pr Laura CALABRESI, Pr Guido FRANCESCHINI. Familial LCAT deficiency. Orphanet. March 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79293.
          3. Anastasopoulou C & Nguyen L. Lecithin-Cholesterol Acyltransferase Deficiency. Medscape. August 08, 2016; https://emedicine.medscape.com/article/122958-overview.
          4. Lecithin:Cholesterol Acyltransferase Deficiency. In: Kniffin, CL. Online Mendelian Inheritance of Disease (OMIM). 9/9/2016; https://www.omim.org/entry/245900.
          5. Mahdi Althaf, M. et al. Familial lecithin-cholesterol acyltransferase (LCAT) deficiency; a differential of proteinuria. Journal of Nephropathology. January 2015; 4(1):25-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316582/.

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