Vitamin D and Inborn Errors of Metabolism

Inborn errors of metabolism are produced by an enzymatic alteration that can be fatal or leave serious neurological sequelae. Some of these conditions require specific nutritional treatment to reverse the clinical symptoms. For phenylketonuria, patients must restrict the intake of phenylalanine; for glucose transporter deficiency syndrome type 1, the treatment is a ketogenic diet; and for classic galactosemia, galactose must be eliminated from the diet. Due to nutritional restrictions, there is an increased risk of deficiency of vitamin D and calcium, which could have an effect on plasma vitamin D levels and cause alterations in bone mineral density (BMD) among children and long-term treated patients. According to scientific evidence, the risks of vitamin D deficiency among these patients are similar to those among healthy persons. While the etiology of lower BMD is not entirely clear, it is attributed to a joint effect of underlying pathology and metabolic changes generated by diet therapy. Long-term follow-up is suggested, in addition to verifying that recommendations o critical nutrients are covered. Timely evaluation of plasmatic levels of vitamin D and BMD is suggested to avoid deficiencies or excesses and to grant a better quality of life to persons with these pathologies

Current practices and challenges in the diagnosis and management of pku in Latin America: A multicenter survey

This study aimed to describe the current practices in the diagnosis and dietary management of phenylketonuria (PKU) in Latin America, as well as the main barriers to treatment. We developed a 44-item online survey aimed at health professionals. After a pilot test, the final version was sent to 25 practitioners working with inborn errors of metabolism (IEM) in 14 countries. Our results include 22 centers in 13 countries. Most countries (12/13) screened newborns for PKU. Phenylalanine (Phe) targets at different ages were very heterogeneous among centers, with greater consistency at the 0–1 year age group (14/22 sought 120–240 µmol/L) and the lowest at >12 years (10 targets reported). Most countries had only unflavored powdered amino acid substitutes (10/13) and did not have low-protein foods (8/13). Only 3/13 countries had regional databases of the Phe content of foods, and only 4/22 centers had nutrient analysis software. The perceived obstacles to treatment were: low purchasing power (62%), limited/insufficient availability of low-protein foods (60%), poor adherence, and lack of technical resources to manage the diet (50% each). We observed a heterogeneous scenario in the dietary management of PKU, and most countries experienced a lack of dietary resources for both patients and health professionals.Fil: Poloni, Soraia. Hospital de Clínicas de Porto Alegre; BrasilFil: Dos Santos, Bruna Bento. Universidade Federal do Rio Grande do Sul; Brasil. Hospital de Clínicas de Porto Alegre; BrasilFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Specola, Norma. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Pereyra, Marcela. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Saborío Rocafort, Manuel. Universidad de Costa Rica; Costa RicaFil: Salazar, María Florencia. Universidad de Chile; ChileFil: Leal-Witt, María Jesús. Universidad de Chile; ChileFil: Castro, Gabriela. Universidad de Chile; ChileFil: Peñaloza, Felipe. Universidad de Chile; ChileFil: Wong, Sunling Palma. Hospital Nacional de Niños; Costa RicaFil: Badilla Porras, Ramsés. Hospital Nacional de Niños; Costa RicaFil: Ortiz Paranza, Lourdes. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Sanabria, Marta Cristina. Hospital de Clínicas; ParaguayFil: Vela Amieva, Marcela. Instituto Nacional de Pediatría; MéxicoFil: Morales, Marco. No especifíca;Fil: Caro Naranjo, Amanda Rocío. Pontificia Universidad Javeriana; ColombiaFil: Mahfoud, Antonieta. Pontificia Universidad Javeriana; ColombiaFil: Colmenares, Ana Rosa. Hospital Clinica Caracas-Materno Infantil de Caricuao; VenezuelaFil: Lemes, Aida. Instituto de Seguridad Social; UruguayFil: Sotillo Lindo, José Fernando. Hospital de especialidades Pediátricas “Omar Torrijos Herrera"; PanamáFil: Perez, Ceila. Robert Reid Cabral Children’s Hospital; República DominicanaFil: Martínez Rey, Laritza. Centro Nacional de Genética Médica; CubaFil: Zayas Torriente, Georgina María. Centro de Nutrición e Higiene de los Alimentos del Instituto Nacional de Higiene, Epidemiología y Microbiología; CubaFil: Farret Refosco, Lilia. Hospital de Clínicas de Porto Alegre; BrasilFil: Doederlein Schwartz, Ida Vanessa. Universidade Federal do Rio Grande do Sul; Brasil. Hospital de Clínicas de Porto Alegre; BrasilFil: Cornejo, Veronica. Universidad de Chile; Chil

Efecto de una intervención del estilo de vida en el perfil metabólico de sujetos prepuberales con obesidad

[spa] INTRODUCCIÓN: La obesidad en uno de los mayores factores de riesgo para desordenes metabólicos y cardiovasculares. El exceso de peso ganado durante la infancia aumenta el riesgo de enfermedad en el adulto, sin embargo revirtiendo esta condición tempranamente se reduce el riesgo futuro mejorando la calidad de vida de los individuos. OBJETIVOS: Una intervención en el estilo de vida de individuos prepuberales con obesidad podría provocar cambios en signaturas metabólicas en paralelo con mejoras del IMC. Nuestro objetivo principal fue determinar los efectos de una intervención en el estilo de vida en el perfil metabolómico tanto del plasma como de la orina en individuos prepuberales con obesidad. MÉTODOS: Estudio longitudinal prospectivo en 40 individuos prepuberales con obesidad (IMC > 2 D.E.) entre las edades de 7 a 10 años. La intervención fue principalmente educacional, focalizada a los individuos y sus familias durante 6 meses. Se analizaron parámetros nutricionales, antropométricos y bioquímicos antes y después de la intervención. También se realizó metabolómica no dirigida para muestras de plasma mediante LC-MS y dirigida para muestras de orina mediante RMN, obteniendo así un perfil metabólico completo antes y después de la intervención. RESULTADOS: La intervención disminuyó el IMC de 3,55 D.E. (3,30 - 3,79) a 3,09 D.E. (2,86 - 3,32), la circunferencia de cintura de 83 cm (79,6 - 85,8) a 81 cm (77,8- 84,5) y los niveles de HbA1c de 5,4% (5,3 - 5,4) a 5,2% (5,2 - 5,3), las variables se analizaron mediante Test t-Student pareado. Se disminuyó la ingesta de calorías, carbohidratos, azúcares libres y grasas. No se logró modificar las horas de actividad física. En el perfil metabólico del plasma se identificaron 2581 picos y se aplicó el Análisis de Componentes Principales para consolidarlos en 8 componentes (PC). El PC1 fue el único factor que tuvo diferencia después de la intervención (p= 0,008) incluso ajustando por comparaciones múltiples. El PC1 está compuesto por metabolitos relacionados con el metabolismo de esfingolípidos observando una disminución de los niveles circulantes de las especies identificadas. En relación al perfil metabólico de las muestras de orina, se identificaron 32 metabolitos. Los niveles de TMAO fueron significativamente menores después de la intervención (FDR q < 0,05). El cambio en los niveles de TMAO se relacionaron inversamente con el cambio en la ingesta de fibra. CONCLUSIONES: Una intervención en el estilo de vida reduce el IMC D.E. y modifica el metaboloma del plasma y de la orina. En particular, la intervención disminuyó los niveles de ceramidas, asociadas estrechamente con enfermedades metabólicas. Además, se redujeron los niveles de TMAO, biomarcador de riesgo cardiovascular. Por lo tanto podemos sugerir que una intervención en el estilo de vida de individuos prepuberales con obesidad puede ser un importante mecanismo para reducir el riesgo de enfermedades metabólicas y cardiovasculares.[eng] BACKGROUND: Obesity is one of the major risk factor for metabolic disorders, and its global prevalence has increased exponentially in the last decades. Excessive weight gained during early childhood increases long-term risk; however, reversing this condition during early-life reduces risk, improving children’s quality of life. OBJECTIVE: We hypothesized that a lifestyle intervention in obese prepubertal children would result in differential metabolic signatures, in parallel to improvements in BMI. Our aim was to determine the changes in the plasma and urine metabolomics profiles induced by the intervention. METHOD: Longitudinal prospective study of 40 obese (BMI >2 SDS) prepubertal children ages 7 to 10. The lifestyle intervention was primarily educational, focused on children and family for 6 months. We analyzed nutritional, anthropometrics and biochemical parameters before and after intervention program. Untargeted metabolomics was applied to analyze plasma samples by LC-MS and targeted metabolomics to urine samples by nuclear magnetic resonance and to obtain a comprehensive metabolic profile at baseline and after intervention. RESULTS: The intervention decreased BMI 3.55 SDS (3.30-3.79) vs 3.09 SDS (2.86-3.32), waist- circumference 83 cm (79.6-85.8) vs 81 cm (77.8-84.5), and HbA1c levels 5.4% (5.3-5.4) vs 5.2% (5.2-5.3) using 2-tails paired student t-test. After 6 month decreased calories, carbohydrates, sugars and fat intakes. Was not achieved modify the physical activity hours. In relation with plasma metabolic profile, identified 2581 features and principal component analysis was applied to consolidate them into 8 principal factors (PC). PC1 differed between pre- and post- intervention (p=0.008), and significance was maintained after adjusting for multiple comparisons; PC1 was characterized by metabolites related with sphingolipid metabolism decreasing its levels after intervention. Urine metabolomics identified 32 metabolites. Trimethylamineoxide (TMAO) levels were significantly lower after intervention (FDR q< 0.05). The change in TMAO was inversely relationated with changes in fiber intake CONCLUSION: A 6-month lifestyle intervention able to reduce BMI-SDS and change the plasma and urine metabolome. In particular, the intervention reduced ceramides levels related to metabolic diseases and TMAO levels, a major cardiovascular risk factor. Therefore, these data suggest that the lifestyle intervention improves the metabolic and cardiovascular risk profiles in prepubertal obese children

Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity

Sex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels and lower adiponectin levels. Moreover, we have recently elucidated the molecular mechanisms by which TNFα and adiponectin regulate hepatic SHBG production. The main objective of this study was to assess if the adult associations between TNFα, adiponectin, and SHBG are present in prepubertal children. We determined several morphometric and biochemical parameters in normal-weight (n =15) and obese prepubertal (n =51) children, as well as quantified plasma SHBG, TNFα receptor 1 (TNFα-R1), and adiponectin levels. Our results showed that prepubertal children with obesity had decreased plasma SHBG levels compared to normal-weight controls (67 nmol/L vs 172 nmol/L). Importantly, SHBG plasma levels correlated significantly (P < 0.05) with TNFα (negatively, ßstd= − 0.31) and adiponectin (positively, ßstd= 0.58) suggesting an important role of these two cytokines in determining plasma SHBG levels in prepubertal children. Our results suggest that plasma adiponectin levels may play a more important role than TNFα in influencing plasma SHBG levels in our prepubertal population with obesity

NTBC Treatment Monitoring in Chilean Patients with Tyrosinemia Type 1 and Its Association with Biochemical Parameters and Liver Biomarkers

Treatment and follow-up in Hereditary Tyrosinemia type 1 (HT-1) patients require comprehensive clinical and dietary management, which involves drug therapy with NTBC and the laboratory monitoring of parameters, including NTBC levels, succinylacetone (SA), amino acids, and various biomarkers of liver and kidney function. Good adherence to treatment and optimal adjustment of the NTBC dose, according to clinical manifestations and laboratory parameters, can prevent severe liver complications such as hepatocarcinogenesis (HCC). We analyzed several laboratory parameters for 15 HT-1 patients over one year of follow-up in a cohort that included long-term NTBC-treated patients (more than 20 years), as well as short-term patients (one year). Based on this analysis, we described the overall adherence by our cohort of 70% adherence to drug and dietary treatment. A positive correlation was found between blood and plasma NTBC concentration with a conversion factor of 2.57. Nonetheless, there was no correlation of the NTBC level with SA levels, αFP, liver biomarkers, and amino acids in paired samples analysis. By separating according to the range of the NTBC concentration, we therefore determined the mean concentration of each biochemical marker, for NTBC ranges above 15–25 μmol/L. SA in urine and αFP showed mean levels within controlled parameters in our group of patients. Future studies analyzing a longer follow-up period, as well as SA determination in the blood, are encouraged to confirm the present findings