LCAT deficiency: a systematic review with the clinical and genetic description of Mexican kindred

Abstract Background LCAT (lecithin-cholesterol acyltransferase) deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). This is the first systematic review evaluating the ethnic distribution of LCAT deficiency, with particular emphasis on Latin America and the discussion of three Mexican-Mestizo probands. Methods A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) 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 included. Results The systematic review revealed 215 cases (154 FLD, 41 FED and 20 unclassified) pertaining to 33 ethnic/racial groups. There was no association between genetic alteration and ethnicity. The mean age of diagnosis was 42 ± 16.5 years, with fish eye disease identified later than familial LCAT deficiency (55 ± 13.8 vs. 41 ± 14.7 years respectively). The prevalence of premature coronary heart disease was significantly greater in FED vs. FLD. In Latin America, 48 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). Of the Mexican probands, one showed a novel LCAT mutation. Conclusions The systematic review shows that LCAT deficiency syndromes are clinically and genetically heterogeneous. No association was confirmed between ethnicity and LCAT mutation. There was a significantly greater risk of premature coronary artery disease in fish eye disease compared to familial LCAT deficiency. In FLD, the emphasis should be in preventing both cardiovascular disease and the 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.

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“LCAT Deficiency: a Systematic Review With the Clinical and Genetic Description of Mexican Kindred”

10.21203/rs.3.rs-402403/v1 ◽

2021 ◽

Author(s):

Roopa Mehta ◽

Daniel Elías-López ◽

Alexandro J. Martagon ◽

Oscar A Pérez-Méndez ◽

Maria Luisa Ordóñez Sánchez ◽

...

Keyword(s):

Systematic Review ◽

Latin America ◽

Premature Coronary Artery Disease ◽

Racial Groups ◽

Premature Coronary Heart Disease ◽

Prisma Statement ◽

Age Of Diagnosis ◽

Artery Disease ◽

Lcat Deficiency ◽

Progression Of Renal Disease

Abstract Background: LCAT deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). In this study the results of the first systematic review evaluating the ethnic distribution of LCAT deficiency are shown, with particular emphasis on Latin America with discussion 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:The systematic review revealed 215 cases (154 FLD, 41 FED and 20 unclassified) pertaining to 33 ethnic/racial groups. There was no association between genetic alteration and ethnicity. The mean age of diagnosis was 42 ± 16.5 years, with FED identified 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. In Latin America, 48 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). Of the Mexican probands, one showed a novel LCAT mutation. Conclusion: The systematic review shows that LCAT deficiency syndromes are clinically and genetically heterogeneous. No association was confirmed between ethnicity and LCAT mutation. There was a significantly greater risk of premature coronary artery disease in FED compared to FLD. In FLD, the emphasis should be in preventing both cardiovascular disease and the 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.

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

10.21203/rs.3.rs-97455/v1 ◽

2020 ◽

Author(s):

Roopa Mehta ◽

Daniel Elías-López ◽

Alexandro J Martagón ◽

Oscar A Pérez-Méndez ◽

María L Ordóñez-Sánchez ◽

...

Keyword(s):

Systematic Review ◽

Novel Mutation ◽

Genetic Admixture ◽

Premature Coronary Artery Disease ◽

Racial Groups ◽

Premature Coronary Heart Disease ◽

Age Of Diagnosis ◽

Artery Disease ◽

Lcat Deficiency ◽

Progression Of Renal Disease

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.

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Using Literature Based Discovery to Gain Insights Into the Metabolomic Processes of Cardiac Arrest

Frontiers in Research Metrics and Analytics ◽

10.3389/frma.2021.644728 ◽

2021 ◽

Vol 6 ◽

Author(s):

Sam Henry ◽

D. Shanaka Wijesinghe ◽

Aidan Myers ◽

Bridget T. McInnes

Keyword(s):

Cardiac Arrest ◽

Survival Rates ◽

Cholesterol Acyltransferase ◽

Eye Disease ◽

Lecithin Cholesterol Acyltransferase ◽

Literature Based Discovery ◽

Lcat Deficiency ◽

Fish Eye ◽

Cardiac Arrest Survival

In this paper, we describe how we applied LBD techniques to discover lecithin cholesterol acyltransferase (LCAT) as a druggable target for cardiac arrest. We fully describe our process which includes the use of high-throughput metabolomic analysis to identify metabolites significantly related to cardiac arrest, and how we used LBD to gain insights into how these metabolites relate to cardiac arrest. These insights lead to our proposal (for the first time) of LCAT as a druggable target; the effects of which are supported by in vivo studies which were brought forth by this work. Metabolites are the end product of many biochemical pathways within the human body. Observed changes in metabolite levels are indicative of changes in these pathways, and provide valuable insights toward the cause, progression, and treatment of diseases. Following cardiac arrest, we observed changes in metabolite levels pre- and post-resuscitation. We used LBD to help discover diseases implicitly linked via these metabolites of interest. Results of LBD indicated a strong link between Fish Eye disease and cardiac arrest. Since fish eye disease is characterized by an LCAT deficiency, it began an investigation into the effects of LCAT and cardiac arrest survival. In the investigation, we found that decreased LCAT activity may increase cardiac arrest survival rates by increasing ω-3 polyunsaturated fatty acid availability in circulation. We verified the effects of ω-3 polyunsaturated fatty acids on increasing survival rate following cardiac arrest via in vivo with rat models.

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