The value of waist circumference as a preditor of cardiovascular risk in adult patients with classic phenylketonuria / Valor del perímetro cintura en la predicción del riesgo cardiovascular en pacientes adultos con fenilcetonuria clásica

Background and aims We aimed to evaluate the differences in some cardiovascular risk (CVR) factors between adult patients without and with phenylketonuria (PKU) and to explore the correlation between waist circumference (WC) and body mass index (BMI) with the previous variables. Methods This was an observational case–control study that included patients older than 18 years with a diagnosis of classic PKU. The controls were age- and sex-matched individuals. We collected demographic, epidemiological, clinical, and laboratory variables, including WC, BMI, and lipid profile parameters. Results A total of 72 patients (25 controls and 47 cases) were included with a mean age of 36 years, of which 45 (62%) were women. Adult PKU patients showed lower high-density lipoprotein cholesterol (HDL-c) and higher triglyceride (TG) levels than the control group. We found an association between WC and uric acid (B=0.024, P=0.013, 95%CI: 0.005–0.043), TG (B=0.768, P=0.024, 95%CI: 0.107–1.428), and HDL-c (B=−0.254, P=0.026, 95%CI: −0.477 to (−0.032)) levels in PKU patients. However, we did not find any trend between WC and uric acid, TG and HDL-c levels that reached statistical significance (P<0.05) in patients without PKU. Conclusions Waist circumference rather than BMI may better represent the CVR in patients with PKU (AU)

Introducción y objetivos Nuestro objetivo fue evaluar las diferencias en algunos factores de riesgo cardiovascular entre pacientes adultos sin y con fenilcetonuria (FCU) y explorar la correlación del perímetro cintura (PC) e índice de masa corporal (IMC) con las variables previas. Métodos Fue un estudio de casos y controles que incluyó pacientes mayores de 18 años con diagnóstico de FCU clásica. Los controles fueron individuos emparejados por edad y sexo. Se recogieron variables demográficas, epidemiológicas, clínicas y de laboratorio, destacando PC, IMC y parámetros del perfil lipídico. Resultados Se reclutaron 72 pacientes (25 controles y 47 casos) con una edad media de 36 años (62% mujeres). Respecto al grupo control, los pacientes adultos con FCU mostraron niveles más bajos de colesterol de lipoproteínas de alta densidad (HDL-c) y más altos de triglicéridos. En los pacientes con FCU, PC se asoció con los niveles de ácido úrico (B=0,024, P=0,013, 95% CI: 0,005-0,043), triglicéridos (B=0,768, P=0,024, 95% CI: 0,107-1.428) y HDL-c (B=−0,254, P=0,026, 95% CI: −0,477–[−0,032]). Sin embargo, no encontramos ninguna tendencia entre WC y dichas variables que alcanzara significación estadística en los pacientes sin FCU. Aunque observamos una buena correlación entre el IMC y PC en pacientes sin y con FCU, el aumento de PC por unidad de aumento de IMC podría ser mayor en estos últimos. Conclusiones Perímetro de cintura podría representar mejor que IMC el riesgo cardiovascular en pacientes con FCU (AU)

The value of waist circumference as a preditor of cardiovascular risk in adult patients with classic phenylketonuria.

BACKGROUND AND AIMS: We aimed to evaluate the differences in some cardiovascular risk (CVR) factors between adult patients without and with phenylketonuria (PKU) and to explore the correlation between waist circumference (WC) and body mass index (BMI) with the previous variables. METHODS: This was an observational case-control study that included patients older than 18 years with a diagnosis of classic PKU. The controls were age- and sex-matched individuals. We collected demographic, epidemiological, clinical, and laboratory variables, including WC, BMI, and lipid profile parameters. RESULTS: A total of 72 patients (25 controls and 47 cases) were included with a mean age of 36 years, of which 45 (62%) were women. Adult PKU patients showed lower high-density lipoprotein cholesterol (HDL-c) and higher triglyceride (TG) levels than the control group. We found an association between WC and uric acid (B=0.024, P=0.013, 95%CI: 0.005-0.043), TG (B=0.768, P=0.024, 95%CI: 0.107-1.428), and HDL-c (B=-0.254, P=0.026, 95%CI: -0.477 to (-0.032)) levels in PKU patients. However, we did not find any trend between WC and uric acid, TG and HDL-c levels that reached statistical significance (P<0.05) in patients without PKU. CONCLUSIONS: Waist circumference rather than BMI may better represent the CVR in patients with PKU.

Association of a Novel Homozygous Variant in ABCA1 Gene with Tangier Disease.

Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral tissues and early coronary disease but with highly variable clinical expression. Herein, we describe a case study of a 59-year-old male patient with features typical of TD, in whom a likely pathogenic variant in the ABCA1 gene was identified by whole-exome sequencing (WES), identified for the first time as homozygous (NM_005502.4: c.4799A>G (p. His1600Arg)). In silico analysis including MutationTaster and DANN score were used to predict the pathogenicity of the variant and a protein model generated by SWISS-MODEL was built to determine how the homozygous variant detected in our patient may change the protein structure and impact on its function. This case study describes a homozygous variant of the ABCA1 gene, which is responsible for a severe form of TD and underlines the importance of using bioinformatics and genomics for linking genotype to phenotype and better understanding and accounting for the functional impact of genetic variations.

The correlation of lipid profile and waist circumference with phenylalanine levels in adult patients with classical phenylketonuria / Correlación del perfil lipídico y el perímetro de cintura con los niveles de fenilalanina en pacientes adultos con fenilcetonuria clásica

Introduction and Objectives Some studies have pointed to a relationship between Phenyketonuria (PKU) and an increased cardiovascular risk (CVR). This study aimed to evaluate the influence of metabolic control on classical CVR factors in adult patients with PKU. Material and methods It was a cross-sectional study conducted in patients older than 18 years with a diagnosis of classical PKU and under strict dietary control. Demographic, epidemiological and laboratory variables related to CVR were collected. The variables of metabolic control were some parameters related to phenylalanine (Phe) plasma levels. Results A total of 47 patients were included with a mean age of 36 ± 10 years of which 30 (64%) were women. Multivariate analysis revealed that range Phe (B = −2.211, P = 0.044, 95%CI: −4.354–(−0.068)) levels were within the model for triglyceride concentrations, while minimum (B = −2.803, P = 0.051, 95%CI: −5.612–0.007) and range (B = −1.515, P = 0.039, 95%CI: −2.945–(−0.084)) Phe levels were within the model for high-density lipoprotein cholesterol concentrations. Median Phe levels showed a stronger correlation with waist circumference (WC) (B = 1.216, P = 0.002, 95%CI: 0.462–1.969) than with body mass index (B = 0.355, P = 0.052, 95%CI: −0.004–0.714). Conclusions High Phe levels and wide Phe fluctuations were related to weight gain, increased WC and lipid profile abnormalities. Systematic CVR assessments and comprehensive monitoring of Phe levels may be desirable to prevent or delay cardiovascular disease in PKU patients (AU)

Introducción y objetivos Algunos estudios señalan una relación entre la fenilcetonuria (PKU) y riesgo cardiovascular (RCV). El objetivo de este estudio fue evaluar la influencia del control metabólico sobre los factores de RCV clásicos en pacientes adultos con PKU. Material y métodos Fue un estudio transversal en pacientes mayores de 18 años con diagnóstico de PKU clásica y bajo control dietético estricto. Se recogieron variables demográficas, epidemiológicas y de laboratorio relacionadas con RCV. Las variables de control metabólico fueron algunos parámetros relacionados con los niveles plasmáticos de fenilalanina (Phe). Resultados Se incluyeron 47 pacientes con una edad media de 36 ± 10 años (64% mujeres). El análisis multivariante reveló que el rango de niveles de Phe (B = −2,211, p = 0,044, IC 95%: −4,354; −0,068) se correlacionó con las concentraciones de triglicéridos, mientras que los niveles mínimos (B = −2,803, p = 0,051, IC 95%: −5,612; 0,007) y el rango (B = −1,515, p = 0,039, IC 95%: −2,945; −0,084) de Phe se correlacionaron con las concentraciones de colesterol ligado a lipoproteínas de alta densidad. La mediana de los niveles de Phe mostró una correlación más fuerte con el perímetro de cintura (B = 1,216, p = 0,002, IC 95%: 0,462; 1,969) que con el índice de masa corporal (B = 0,355, p = 0,052, IC 95%: −0,004; 0,714). Conclusiones Niveles altos y fluctuaciones amplias de Phe se correlacionaron con el aumento de peso corporal, incremento de perímetro de cintura y anomalías del perfil lipídico. La realización de evaluaciones sistemáticas de RCV y un seguimiento exhaustivo de los niveles de Phe podrían ser favorables para prevenir o retrasar la enfermedad cardiovascular en los pacientes con PKU (AU)

The correlation of lipid profile and waist circumference with phenylalanine levels in adult patients with classical phenylketonuria.

INTRODUCTION AND OBJECTIVES: Some studies have pointed to a relationship between Phenyketonuria (PKU) and an increased cardiovascular risk (CVR). This study aimed to evaluate the influence of metabolic control on classical CVR factors in adult patients with PKU. MATERIAL AND METHODS: It was a cross-sectional study conducted in patients older than 18 years with a diagnosis of classical PKU and under strict dietary control. Demographic, epidemiological and laboratory variables related to CVR were collected. The variables of metabolic control were some parameters related to phenylalanine (Phe) plasma levels. RESULTS: A total of 47 patients were included with a mean age of 36±10 years of which 30 (64%) were women. Multivariate analysis revealed that range Phe (B=-2.211, P=0.044, 95%CI: -4.354-(-0.068)) levels were within the model for triglyceride concentrations, while minimum (B=-2.803, P=0.051, 95%CI: -5.612-0.007) and range (B=-1.515, P=0.039, 95%CI: -2.945-(-0.084)) Phe levels were within the model for high-density lipoprotein cholesterol concentrations. Median Phe levels showed a stronger correlation with waist circumference (WC) (B=1.216, P=0.002, 95%CI: 0.462-1.969) than with body mass index (B=0.355, P=0.052, 95%CI: -0.004-0.714). CONCLUSIONS: High Phe levels and wide Phe fluctuations were related to weight gain, increased WC and lipid profile abnormalities. Systematic CVR assessments and comprehensive monitoring of Phe levels may be desirable to prevent or delay cardiovascular disease in PKU patients.