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Complete LCAT Deficiency Disorder

Complete Lecithin Cholesterol Acyltransferase Deficiency Disorder (or Complete LCAT Deficiency Disorder) is an extremely rare genetic disorder. It is inherited in an autosomal recessive manner.

What are the other Names for this Condition? (Also known as/Symptoms)

  • Complete Lecithin Cholesterol Acyltransferase Deficiency Disorder
  • Familial LCAT Deficiency Disorder
  • Norum Disease

What is Complete LCAT Deficiency Disorder? (Definition/Background Information)

  • Complete Lecithin Cholesterol Acyltransferase Deficiency Disorder (or Complete LCAT Deficiency Disorder) is an extremely rare genetic disorder. It is inherited in an autosomal recessive manner
  • The disorder is caused by mutation(s) in the LCAT gene, which is located on the long arm of chromosome 16. The LCAT gene codes for the enzyme lecithin cholesterol acyltransferase, which helps cholesterol from blood and body tissues bind lipoproteins, for transport to the liver
  • When there is a mutation in the LCAT gene, the enzyme may become defective in either its alpha-LCAT activity or in both its alpha- and beta-LCAT activities. The activities differ in the kind of lipoprotein the cholesterol binds to. This causes the deposition of fat in organs, with a primary effect on the eyes and kidneys
  • The signs and symptoms of Complete LCAT Deficiency Disorder can include clouding of the corneas due to fat deposits, progressive malfunction of the kidneys due to fat deposits in the glomeruli, and premature breakdown of red blood cells leading to anemia
  • Kidney failure and vision deterioration are some of the potential complications of Complete LCAT Deficiency Disorder. If LCAT deficiency is partial, the symptoms may be limited only to the eyes and liver
  • A diagnosis of Complete LCAT Deficiency Disorder can be undertaken prenatally or after birth. The diagnosis may involve a physical examination, the assessment of symptoms, evaluation of family medical history, blood and urine tests, and confirmatory genetic testing
  • Complete LCAT Deficiency Disorder cannot be cured; however, the symptoms may be treated. Some of the treatment options include corticosteroid medication for anemia, corneal transplantation for vision defects, dietary restrictions for salt intake, dialysis, and kidney transplantation for any associated progressive kidney dysfunction (if necessary)
  • Individuals with Complete LCAT Deficiency Disorder are reported to have a normal life expectancy, if the condition is diagnosed and managed properly. Nonetheless, a progression to end-stage renal disease may have a poor outcome

Who gets Complete LCAT Deficiency Disorder? (Age and Sex Distribution)

  • Complete LCAT Deficiency Disorder is a very rare condition with an incidence rate of less than 1 in 1 million individuals. So far, only about 70 cases have been reported in the scientific and medical literature
  • The condition is congenital in nature and some of the signs and symptoms may be manifested at birth
  • Both males and females can develop this deficiency disorder
  • No racial and ethnic group preference is noted

What are the Risk Factors for Complete LCAT Deficiency Disorder? (Predisposing Factors)

  • A positive family history of Complete LCAT Deficiency Disorder is a major risk factor for developing the condition, since it is predominantly an inherited disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Complete LCAT Deficiency Disorder? (Etiology)

  • Complete LCAT Deficiency Disorder is caused due to mutation(s) in the LCAT gene. The LCAT gene is located in the long arm of chromosome 16, at the location 22.1 (16q22.1)
    • The gene codes for an enzyme, known as lecithin-cholesterol acyltransferase (LCAT). This enzyme helps cholesterol bind lipoproteins, which helps remove cholesterol from blood and body tissues and facilitates its transport to the liver. The liver then re-distributes the cholesterol
    • The enzyme achieves its function by aiding cholesterol to bind to specific types of lipoprotein, via alpha-LCAT and beta-LCAT activities. Whereas the alpha-LCAT aids in binding of cholesterol to high density lipoprotein (HDL), the beta-LCAT activity helps cholesterol bind to low density and very low density lipoproteins (LDL and VLDL)
    • When a mutation in the LCAT gene affects both LCAT activities, the removal of cholesterol from blood and body tissues is affected, leading to fat deposits in many body parts. The eyes and kidneys are especially susceptible in Complete LCAT Deficiency Disorder
    • On the other hand, mutation(s) in the LCAT gene can also specifically impair the alpha-LCAT activity. This is known as a partial deficiency or fish-eye disease
  • Both complete and partial deficiencies of LCAT enzyme are inherited in an autosomal recessive fashion, in which an individual inherits a defective copy of the gene from each parent. The disorder does not manifest itself unless an individual has both defective copies of the gene in all of his/her cells

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

What are the Signs and Symptoms of Complete LCAT Deficiency Disorder?

The signs and symptoms of Complete LCAT Deficiency Disorder include:

  • Progressive malfunction of the kidneys, proteinuria, and kidney failure
  • Hemolytic anemia due to premature breakdown of red blood cells leading to:
    • Washed-out appearance (pale appearance)
    • Fatigue and weakness
    • Dizziness
  • Atherosclerosis (fat deposition on the walls of the arteries)
  • Fat deposit in the corneas in eyes causing them to cloud and become opaque
    • Eyes having whitish appearance
    • Progressive eye clouding leading to vision abnormalities
  • Enlarged liver (hepatomegaly), enlarged spleen (splenomegaly), and enlarged lymph nodes (lymphadenopathy) are noted in some individuals

Note: In partial LCAT Deficiency Disorder, the major symptoms involve the eyes and the liver.

How is Complete LCAT Deficiency Disorder Diagnosed?

An accurate diagnosis of Complete LCAT Deficiency Disorder may be made through the following tests and procedures:

  • A complete physical examination
  • An assessment of symptoms
  • An evaluation of family history
  • Blood tests to check for:
    • Anemia
    • Cholesterol and lipoprotein levels
  • Urine analysis to analyse how well the kidneys are functioning
  • Eye exams to check for clouding of the corneas and check for vision impairments
  • Genetic testing of LCAT gene and functional analysis of the enzyme
  • Kidney biopsy to observe fat deposits in the glomeruli (a cluster of tiny blood vessels that help remove waste from blood)

Note: It is possible to diagnose the condition prenatally, particularly when the disorder runs in the family and expecting parents seek further information.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Complete LCAT Deficiency Disorder?

Some of the potential complications of Complete LCAT Deficiency Disorder include:

  • Progressive deterioration of kidney function leading to kidney failure
  • Severe vision defects due to clouding of the corneas

How is Complete LCAT Deficiency Disorder Treated?

The treatment options for Complete LCAT Deficiency Disorder depend on the severity of malfunction of the organs:

  • For anemia, symptomatic treatments to improve red blood cell numbers in blood are recommended. This may be achieved through:
    • Corticosteroids medication
    • Intravenous immunoglobulin treatment
    • Blood transfusions
    • Plasmapheresis: Plasma, which contains antibodies that destroys red blood cells, is removed from blood and donor (normal) plasma added. This new blood is introduced into the body through a blood transfusion procedure
    • Surgical removal of the spleen, for severe cases
  • For proteinuria (protein in urine), restricting salt and protein in the diet may be recommended
  • If kidney function has deteriorated, dialysis may be recommended
  • In severe cases of kidney malfunction/failure, kidney transplantation may be a treatment option
  • Progressive corneal opacity and vision loss may be addressed by corneal transplantation

How can Complete LCAT Deficiency Disorder be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Complete LCAT Deficiency Disorder, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Complete LCAT Deficiency Disorder
  • Regular medical screening at periodic intervals with tests and physical examinations are strongly recommended

What is the Prognosis of Complete LCAT Deficiency Disorder? (Outcomes/Resolutions)

The prognosis of Complete LCAT Deficiency Disorder is reported to be variable.

  • The life expectancy of individuals with the disorder is expected to be normal, if it is managed properly
  • However, if the kidney function continues to deteriorate progressively, it may culminate in end-stage renal disease and the outcome may be unfavorable
  • Lifestyle adjustments may be needed when the affected individuals continue to have progressive vision loss

Additional and Relevant useful Information for Complete LCAT Deficiency Disorder:

Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information:


What are some Useful Resources for Additional Information?

Genetic and Rare Diseases (GARD) Information Center
PO Box 8126 Gaithersburg, MD 20898-8126
Toll-Free: (888) 205-2311
TTY: (888) 205-3223
International Telephone Access Number: (301) 251-4925
Fax: (301) 251-4911
Website: http://rarediseases.info.nih.gov

National Organization for Rare Disorders (NORD)
55 Kenosia Avenue Danbury, CT 06810
Phone: (203) 744-0100
Toll-Free: (800) 999-6673
Fax: (203) 798-2291
Email: orphan@rarediseases.org
Website: http://www.rarediseases.org

References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/condition/complete-lcat-deficiency (accessed on July 15, 2016)

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=79293 (accessed on July 15, 2016)

http://disorders.eyes.arizona.edu/disorders/lcat-deficiency (accessed on July 15, 2016)

https://www.icm-mhi.org/en/health-care-and-services/cardiovascular-diseases/lecithin-cholesterol-acyltransferase-lcat-deficiency (accessed on July 15, 2016)

Helpful Peer-Reviewed Medical Articles:

Kuivenhoven, J. A., Pritchard, H., Hill, J., Frohlich, J., Assmann, G., & Kastelein, J. (1997). The molecular pathology of lecithin: cholesterol acyltransferase (LCAT) deficiency syndromes. Journal of lipid research,38(2), 191-205.

Ayyobi, A. F., McGladdery, S. H., Chan, S., Mancini, G. J., Hill, J. S., & Frohlich, J. J. (2004). Lecithin: cholesterol acyltransferase (LCAT) deficiency and risk of vascular disease: 25 year follow-up. Atherosclerosis, 177(2), 361-366.

Bujo, H., Kusunoki, J., Ogasawara, M., Yamamoto, T., Ohta, Y., Shimada, T., ... & Yoshida, S. (1991). Molecular defect in familial lecithin: cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease. Biochemical and biophysical research communications, 181(3), 933-940.

Savel, J., Lafitte, M., Pucheu, Y., Pradeau, V., Tabarin, A., & Couffinhal, T. (2012). Very low levels of HDL cholesterol and atherosclerosis, a variable relationship–a review of LCAT deficiency. Vasc Health Risk Manag, 8, 357-361.

Funke, H., von Eckardstein, A., Pritchard, P. H., Hornby, A. E., Wiebusch, H., Motti, C., ... & Gerdes, U. (1993). Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease. Journal of Clinical Investigation, 91(2), 677.

Sakai, N., Vaisman, B. L., Koch, C. A., Hoyt, R. F., Meyn, S. M., Talley, G. D., ... & Santamarina-Fojo, S. (1997). Targeted disruption of the mouse lecithin: cholesterol acyltransferase (LCAT) gene generation of a new animal model for human LCAT deficiency. Journal of Biological Chemistry, 272(11), 7506-7510.

Rader, D. J., Ikewaki, K., Duverger, N., Schmidt, H., Pritchard, H., Frohlich, J., ... & Zech, L. (1994). Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease. Journal of Clinical Investigation, 93(1), 321.

Ng, D. S., Francone, O. L., Forte, T. M., Zhang, J., Haghpassand, M., & Rubin, E. M. (1997). Disruption of the murine lecithin: cholesterol acyltransferase gene causes impairment of adrenal lipid delivery and up-regulation of scavenger receptor class B type I. Journal of Biological Chemistry, 272(25), 15777-15781.

Frohlich, J., Godolphin, W. J., Reeve, C. E., & Evelyn, K. A. (1978). Familial LCAT Deficiency Report of Two Patients from a Canadian Family of Italian and Swedish Descent. Scandinavian Journal of Clinical and Laboratory Investigation, 38(sup150), 156-161.

McLean, J., Wion, K., Drayna, D., Fielding, C., & Lawn, R. (1986). Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression. Nucleic acids research, 14(23), 9397-9406.