Fish-eye disease

Fish-eye disease is a genetic disorder involving a deficiency in lecithin—cholesterol acyltransferase (LCAT) metabolism.[1] While LCAT metabolism in familial LCAT deficiency is fully inactive, patients with fish-eye disease only have a partial deficiency of LCAT.[1] Carlson and Philipson found that the disease was named so because the cornea of the eye was so opaque or cloudy with dots of cholesterol that it resembled a boiled fish.[2]

The disorder is inherited in an autosomal recessive manner.[3] Therefore, both copies of the gene in each cell must have a mutation; if an individual only carry one copy of the mutated gene, they typically do not show symptoms.[4]

Fish-eye disease is characterized by abnormalities like visual impairment, plaques of fatty material, and dense opacification.[2][3] It is uncertain if LCAT deficiencies are linked to coronary artery disease.[3]

Biochemistry of LCAT

The LCAT glycoprotein produces lysophosphatidylcholine and cholesterol ester and binds to lipoproteins after being secreted by the liver.[2] Usually the enzyme produced is responsible for cholesterol ester formation and high density lipoprotein (HDL) metabolism, but in fish-eye disease the enzyme cannot esterify, or make the acid into an alkyl, cholesterol in HDL particles.[3] However, there is only a partial deficiency because the enzyme remains active on the cholesterol particles in very low density lipoproteins (VLDL) and low density lipoproteins (LDL).[3] The opaqueness of the eye is caused by the deposit of lipids onto the cornea.[3]

Genetics

Mutations in the LCAT gene, which is localized in the q21–22 region of chromosome 16, cause fish-eye disease.[1] The mutation in the LCAT gene is homozygous for a Thr123→Ile mutation or Pro10→Leu mutation.[5] New mutations have been identified as homozygosity for an A2205→G nucleotide substitution in exon 4 of the LCAT gene which is predicted to be the cause of an Asp131→Asn substitution.[3]

References

  1. 1 2 3 Koster, H; Savoldelli, M; Dumon, M. F.; Dubourg, L; Clerc, M; Pouliquen, Y (1992). "A fish-eye disease-like familial condition with massive corneal clouding and dyslipoproteinemia. Report of clinical, histologic, electron microscopic, and biochemical features". Cornea. 11 (5): 452–64. doi:10.1097/00003226-199209000-00016. PMID 1424675.
  2. 1 2 3 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. PMID 9162740.
  3. 1 2 3 4 5 6 7 Kuivenhoven, J. A.; van Voorst tot Voorst EJ; Wiebusch, H; Marcovina, S. M.; Funke, H; Assmann, G; Pritchard, P. H.; Kastelein, J. J. (1995). "A unique genetic and biochemical presentation of fish-eye disease". Journal of Clinical Investigation. 96 (6): 2783–91. doi:10.1172/JCI118348. PMC 185988Freely accessible. PMID 8675648.
  4. ↑ Kaneshiro, N.K. (2014). "Autosomal Recessive". National Institutes of Health, Medline Plus.
  5. ↑ Contacos, C; Sullivan, D. R.; Rye, K. A.; Funke, H; Assmann, G (1996). "A new molecular defect in the lecithin: Cholesterol acyltransferase (LCAT) gene associated with fish eye disease". Journal of lipid research. 37 (1): 35–44. PMID 8820100.
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