Low levels of High Density Lipoprotein (HDL) and Corneal Opacity Caused by Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency

Introduction: Fish Eye Disease (FED) is a rare genetic disorder with less than 50 cases described worldwide thus far. Mutations in the LCAT gene cause lecithin-cholesterol acyltransferase (LCAT) deficiency, resulting clinically in corneal opacifications (“fish eye”) and dyslipidemia (mainly low HDL). We hereby describe a case of a patient with clinically suspected FED further supported by genetic mutation analysis.

Methods: A 64 year old male known to have low levels of High Density Lipoprotein (HDL) and high levels of Low Density Lipoprotein (LDL) and Triglycerides for many years was recently evaluated for new visual impairment. Corneal opacifications raised suspicion of a metabolic disorder, specifically FED. A blood sample was drawn and DNA was extracted from peripheral leukocytes using the “salt precipitation” technique. Subsequently, Polymerase Chain Reaction (PCR) amplified the specific LCAT gene which was further sent for complete nucleotide sequencing. Finally, mutation analysis performed by different well-established tools was used to elucidate the possible effects on protein function.

Results: The PCR reaction produced the complete LCAT gene as observed by gel electrophoresis. Deoxyribonucleic acid (DNA) sequencing of the complete gene showed only one missense mutation, substituting guanine (G) with adenine (A), thus resulting in the amino acid change- A117T. The effect of the above nucleotide substitution on protein function was assessed by SIFT analysis to be a tolerated mutation. Conversely, the Mutation Taster study concluded it to be a known disease causing mutation.

Conclusions: We describe a case of a patient with a clinically suspected genetic disorder, reinforced by DNA sequencing and mutation analysis. This provides a clear example of a new era- the era of Precision Medicine. Proven genetic mutations with adequate clinical correlation can provide patient tailored therapeutic options, such as enzymatic supplementation for our patient, and early diagnosis of other family members.