Familial lecithin-cholesterol acyltransferase deficiency: If so rare, why so frequent in the state of Piauí, northeastern Brazil?

Lecithin-cholesterol acyltransferase (LCAT), an enzyme that participates in lipoprotein metabolism, plays an important role in cholesterol homeostasis. Mutations in the LCAT gene can cause two rare genetic disorders: familial LCAT deficiency (FLD), which is characterized by corneal opacities, normocytic anemia, dyslipidemia, and proteinuria progressing to chronic renal failure, and fish-eye disease (FED), which causes dyslipidemia and progressive corneal opacities. Herein, we report six suspected cases of FLD in the backlands of Piauí, located in northeast Brazil. A genetic diagnosis was performed in index cases. Among these, a further investigation was performed to identify new cases in the families. In addition, molecular analyses were performed to verify the levels of consanguinity within families and the existence of a genetic relationship between them. All six index cases were confirmed as FLD with an identical mutation (c.803G > A, p.R268H). The genetic investigation confirmed another 7 new cases of FLD, 52 heterozygous and 6 individuals without mutations. The rate of consanguinity revealed that marriages within the family did not contribute to the high number of FLD cases within the restricted region. The elders of each family (patriarchs and matriarchs) were subjected to a kinship analysis and were more genetically related to each other than the control group. Bayesian analysis was implemented to confirm the hypothesis of connectivity among patriarchs and matriarchs and indicated that they were genetically more related to each other than would be randomly expected, thus suggesting the occurrence of a possible founder effect in these families.

Triglyceride glucose index as a tool to motivate early lifestyle modification in young adults at diabetes risk: The Baependi Heart Study.

Considering that the incidence of type 2 diabetes mellitus (T2DM) has been increasing especially in developing countries and becoming a global public health problem, this study aims to evaluate the association between triglyceride glucose index (TyG) - which is a mathematical product of the fasting blood glucose and triglyceride levels - and incident T2DM in an adult sample in the Baependi Heart Study (BHS). The data were from the BHS cohort consisting of two periods: cycle 1 (2005-2006; n = 1712; 119 families) and cycle 2 (2010-2013; n = 3017; 127 families). A total of 1121 individuals (both sexes, 18-100 years) were selected if they were assessed in both cycles and not diagnosed with T2DM at baseline (cycle 1). Our findings showed that a participant's risk of developing T2DM increased almost 10 times for a one-unit increase in the TyG (odds ratio OR = 10.17, 95% CI, 7.51-13.93). The association when stratified by age was OR = 28.13 [95% CI, 14.03-56.41] for young adults, meaning that the risk of developing T2DM increased more than 28 times for a one-unit increase in the TyG. For the other groups, young middle-aged adults, old middle-aged adults, and seniors, we found OR = 4.84 [95% CI, 2.91-8.06], OR = 28.73 [95% CI, 10.63-77.65, and OR = 9.88 [95% CI, 3.16-30.90], respectively. A higher TyG implies a significant increase in the risk of developing T2DM, which could be an important screening tool to target early lifestyle intervention in Brazil.

Acute exercise in treated phenylketonuria patients: Physical activity and biochemical response.

BACKGROUND: In phenylketonuria, dietary treatment prevents most of the severe brain disease. However, patients have to follow a diet restricted in several natural components, what may cause decreased bone density and obesity. Exercise is known to improve both mental functioning and bone density also avoiding obesity, and could optimize aspects of central and peripheral outcome, regardless changes in phenylalanine (Phe) levels. However, the acute effects of exercise on metabolic parameters in phenylketonuria patients are unknown and thereby long-term adaptations are unclear. Therefore, this study aimed to evaluate patients' basal metabolic rate (BMR), and their acute response to an aerobic exercise session on plasma concentrations of Phe, tyrosine (Tyr), and branched-chain amino acids (BCAA), as well as metabolic and hormonal responses. METHODS: Five early- and four late diagnosed phenylketonuria patients aged 21 ± 4 years and 17 sex-, age-, and BMI-matched controls were evaluated for BMR, peak oxygen consumption (VO2peak) and plasma amino acid, glucose, lipid profile and hormonal levels. At least one week later, participants performed a 30-min aerobic exercise session (intensities individually calculated using the VO2peak results). Blood samples were collected in fasted state (moment 1, M1) and immediately after a small breakfast, which included the metabolic formula for patients but not for controls, and the exercise session (moment 2, M2). RESULTS: Phenylketonuria patients and controls showed similar BMR and physical capacities. At M1, patients presented higher Phe concentration and Phe/Tyr ratio; and lower levels of BCAA and total cholesterol than controls. Besides that, poorly controlled patients tended to stay slightly below the prescribed VO2 during exercise. Both patients and controls showed increased levels of total cholesterol and LDL at M2 compared with M1. Only controls showed increased levels of Tyr, lactate, and HDL; and decreased Phe/Tyr ratio and glucose levels at M2 compared to values at M1. CONCLUSIONS: Acute aerobic exercise followed by a Phe-restricted breakfast did not change Phe concentrations in treated phenylketonuria patients, but it was associated with decreased Phe/Tyr only in controls. Further studies are necessary to confirm our results in a higher number of patients.