LCAT Deficiency in Amerindian Populations: A Systematic Review With the Clinical and Genetic Description of Mexican Kindred

Abstract Background: LCAT deficiency is a rare disease, characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). There is little knowledge of LCAT deficiency syndromes in Amerindian populations. We present the results of the first systematic review evaluating the ethnic distribution of LCAT deficiency, with particular emphasis on Latin America and discuss the case histories of three Mexican-Mestizo probands. Methods: A systematic review was conducted following the PRISMA Statement in Pubmed and SciELO. Articles which described subjects with LCAT deficiency syndromes and an assessment of the ethnic group to which the subject pertained, were considered for analysis. Results: In our region, 47 cases of LCAT deficiency have been published from six countries (Argentina (1 unclassified), Brazil (38 FLD), Chile (1 FLD), Columbia (1 FLD), Ecuador (1 FLD) and Mexico (4 FLD, 1 FED and 1 unclassified). In Mexico, one of the FLD probands’ showed a novel mutation; this patient came from an isolated village in the south of Mexico, with little genetic admixture in this region.The systematic review revealed 215 cases of LCAT deficiency (154 FLD, 41 FED and 20 unclassified) in at least 33 ethnic/racial groups (predominantly Caucasian). In addition, at least 138 different mutations in the LCAT gene have been identified. There was no association between genetic alteration and ethnicity. The mean age of diagnosis was 42 ± 16.5 years, with FED identified significantly later than FLD (55 ± 13.8 vs. 41 ± 14.7 years respectively). The prevalence of premature coronary heart disease was significantly greater in FED vs. FLD (p=0.00). Conclusion: The systematic review shows that LCAT deficiency syndromes are clinically and genetically heterogeneous. We were unable to confirm any association between ethnicity and LCAT mutation. However, we were able to show a significantly greater risk of premature coronary artery disease in FED compared to FLD. In FLD, the emphasis should be in preventing progression of renal disease, while in FED, cardiovascular risk management should be the priority. The LCAT mutations discussed in this article are the only ones reported in the Mexican- Amerindian population.