Background: In patients with phenylketonuria (PKU), a low-phenylalanine (Phe) diet supplemented w... more Background: In patients with phenylketonuria (PKU), a low-phenylalanine (Phe) diet supplemented with lowprotein foods and a Phe-free amino acid mixture favors a dietary intake rich in carbohydrates, but little is known about how these molecules are metabolized in this setting. The objective of the present study was to analyze carbohydrate metabolism in patients with hyperphenylalaninemia. Methods: We conducted a multicenter cross-sectional study to investigate biochemical markers of basal and postprandial carbohydrate metabolism in PKU patients according to age, Phe tolerance, waist circumference and body mass index (BMI), diet, tetrahydrobiopterin (BH4) supplementation, and adherence to treatment. Basal biomarkers and anthropometric parameters were also evaluated in patients with mild hyperphenylalaninemia (MHPA) and in healthy controls. Results: A total of 83 patients aged 4-52 years were studied; 68.7% had PKU and 31.3% had MHPA. 68 healthy controls of similar sex and age were also evaluated Metabolic control was adequate in 71.9% of PKU patients. Fasting glucose levels (mean 80.77 ± 8.06 mg/dL) were high in just one patient, but fasting insulin levels, with a mean of 12.74 ± 8.4 mIU/L, were altered in 15 PKU patients (26.3%) and markedly higher than in patients with MPHA (p = 0.035). Fasting insulin levels and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were significantly higher than in healthy controls and correlated with body mass index, waist circumference, age, and also showed statistically significant differences according to diagnosis and Phe tolerance (p < 0.05). Patients under BH4 therapy had lower insulin levels and HOMA-IR. A higher mean carbohydrate intake from AA mixtures was observed in classic PKU patients. The caloric intake in the form of carbohydrates was also higher in PKU than MHPA patients (p = 0.038) and it was correlated with basal insulin (rho = 0.468, p = 0.006), HOMA-IR (rho = 0.423, p = 0.02), BMI (rho 0.533, p = 0.002), and waist circumference (rho 0.584, p = 0.0007). Conclusions: This study shows that PKU patients are at risk of carbohydrate intolerance and insulin resistance, more evident in adults and overweight patients, probably related to their higher caloric intake in form carbohydrate content. A higher dependency of AA mixtures was demonstrated in PKU patients.
The present work describes the value of genetic analysis as a confirmatory measure following the ... more The present work describes the value of genetic analysis as a confirmatory measure following the detection of suspected inborn errors of metabolism in the Spanish newborn mass spectrometry screening program. One hundred and forty-one consecutive DNA samples were analyzed by next-generation sequencing using a customized exome sequencing panel. When required, the Illumina extended clinical exome panel was used, as was Sanger sequencing or transcriptional profiling. Biochemical tests were used to confirm the results of the genetic analysis. Using the customized panel, the metabolic disease suspected in 83 newborns (59%) was confirmed. In three further cases, two monoallelic variants were detected for two genes involved in the same biochemical pathway. In the remainder, either a single variant or no variant was identified. Given the persistent absence of biochemical alterations, carrier status was assigned in 39 cases. False positives were recorded for 11. In five cases in which the biochemical pattern was persistently altered, further genetic analysis allowed the detection of two variants affecting the function of BCAT2, ACSF3, and DNAJC12, as well as a second, deep intronic variant in ETFDH or PTS. The present results suggest that genetic analysis using extended next-generation sequencing panels can be used as a confirmatory test for suspected inborn errors of metabolism detected in newborn screening programs. Biochemical tests can be very helpful when a diagnosis is unclear. In summary, simultaneous genomic and metabolomic analyses can increase the number of inborn errors of metabolism that can be confirmed following suggestive newborn screening results.
Importancia del agua mineral natural como aporte de nutrientes esenciales Natural mineral water. ... more Importancia del agua mineral natural como aporte de nutrientes esenciales Natural mineral water. Essential nutrients Maraver F (1-2) , Vitoria I (3) , Morer C (4-2) , Armijo F (1-2)
International Journal of Food Science, Nutrition and Dietetics, 2015
Fluoride has multiple mechanisms of action [5]. First, the hydroxyapatite crystals in the enamel ... more Fluoride has multiple mechanisms of action [5]. First, the hydroxyapatite crystals in the enamel become fluorapatite crystals, which are more resistant to decalcification. This chemical reaction is reversible and depends on the concentration of fluoride and acidity in the environment of the tooth enamel. Thus, the hydroxyapatite crystal begins to dissolve when the pH is less than 5.5, whereas fluorapatite dissolves when the pH is less than 4.5
Natural sources of protein and some vitamins and minerals are limited in phenylketonuria (PKU) tr... more Natural sources of protein and some vitamins and minerals are limited in phenylketonuria (PKU) treated patients, who should receive optimal supplementation although this is not yet fully established. We conducted a cross-sectional observational multicenter study including 156 patients with hyperphenylalaninemia. Patients were stratified by age, phenotype, disease detection and type of treatment. Annual median blood phenylalanine (Phe) levels, Phe tolerance, anthropometric measurements, and biochemical parameters (total protein, prealbumin, electrolytes, selenium, zinc, B12, folic acid, ferritin, 25-OH vitamin D) were collected in all patients. 81.4% of patients had biochemical markers out of recommended range but no clinical symptoms. Total protein, calcium, phosphorus, B12, ferritin, and zinc levels were normal in most patients. Prealbumin was reduced in 34.6% of patients (74% with PKU phenotype and 94% below 18years old), showing almost all (96.3%) an adequate adherence to diet. Selenium was diminished in 25% of patients (95% with PKU phenotype) and also 25-OHD in 14%. Surprisingly, folic acid levels were increased in 39% of patients, 66% with classic PKU. Phosphorus and B12 levels were found diminished in patients with low adherence to diet. Patients under BH4 therapy only showed significant lower levels of B12. This study shows a high percentage of prealbumin and selenium deficiencies as well as an increased level of folic acid in PKU treated patients, which should lead us to assess an adjustment for standards supplements formulated milks.
Despite a strict dietary control, patient with hyperphenylalaninemia or phenylketonuria may show ... more Despite a strict dietary control, patient with hyperphenylalaninemia or phenylketonuria may show cognitive and/or behavioral disorders. These comorbid deficits are of great concern to patients, families, and health organizations. However, biomarkers capable of detecting initial stages of neurological damage are not commonly employed. The pathogenesis of phenylketonuria is complex in nature. Increasingly, the role of oxidative stress has gained acceptance and biomarkers reflecting oxidative damage to the brain and easily accessible in peripheral biofluids have been validated using mass spectrometry techniques. In the present review, the role of oxidative stress in the pathogenesis of phenylketonuria and hyperphenylalaninemia has been updated. Moreover, we report on newly validated brain-specific lipid peroxidation biomarkers and inform on their relevance in the detection and monitoring of neurological damage in phenylketonuric patients. In preliminary studies, a correlation between lipid peroxidation biomarkers and neurological dysfunction in patients with PKU was reported. However, there is a need of adequately powered trials to confirm the validity of these biomarkers for early detection of brain damage, initiation of treatment, and reliably monitor evolving disease both in phenylketonuria and hyperphenylalaninemia.
Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providin... more Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providing sufficient energy to avoid catabolism and to limit production of methylmalonic acid. The goal is to achieve normal growth, good nutritional status and the maintenance of metabolic stability. Aim To describe the dietary management of patients with MMA across Europe. Methods A cross-sectional questionnaire was sent to European colleagues managing inherited metabolic disorders (IMDs) (n=53) with 27 questions about the nutritional management of organic acidaemias. Data were analysed by different age ranges (0–6 months; 7–12 months; 1–10 years; 11–16 years; >16 years). Results Questionnaires were returned from 53 centres. Twenty-five centres cared for 80 patients with MMA vitamin B12 responsive (MMAB12r) and 43 centres managed 215 patients with MMA vitamin B12 non-responsive (MMAB12nr). For MMAB12r patients, 44% of centres (n=11/25) prescribed natural protein below the World Health Organ...
Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affect... more Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. Methods: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. Results: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m 2. The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-Lhomocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. Conclusions: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients.
Se ha revisado la composición de 164 bebidas vegetales disponibles en España a partir del etiquet... more Se ha revisado la composición de 164 bebidas vegetales disponibles en España a partir del etiquetado nutricional del envase y de las páginas web de los fabricantes. Se ha comparado con la composición de la leche de vaca y de la fórmula infantil. Además, se ha revisado la patología nutricional asociada con el consumo de bebidas vegetales en lactantes y niños mediante una búsqueda bibliográfica en Medline y EMBASE desde 1990 basada en las palabras clave “plant-based beverages” o “rice beverages” o “almond beverages” o “soy beverages” y “infant” o “child”.
INTRODUCTION: An appropriate magnesium intake has proved to have beneficial effects on bone healt... more INTRODUCTION: An appropriate magnesium intake has proved to have beneficial effects on bone health, reduce insulin resistance and prevent atherosclerosis. Our objective was to determine the concentration of magnesium in bottled mineral water in Spain and assess its daily contribution to dietary recommendations.MATERIAL-METHODS: We used ion chromatography to analyse the magnesium concentrations of 97 spanish natural mineral waters.RESULTS - CONCLUSIONS: The average magnesium concentration of 97 brands of Spanish natural mineral water was 16.2 mg/L (range: 0.1-141.2 mg/L). Of these, 33 contained between 15 and 45 mg/L of magnesium and four contained over 45 mg/L.Assuming water consumption is as recommended by the European Food Safety Agency, water containing 15 to 45 mg/L of magnesium provides between 9 and 76.5% of the recommended intake of magnesium for children aged one to thirteen, up to 25.7% in adolescents, between 7.5 and 25.7% for adults, and up to 27% for lactating women. Wat...
BACKGROUND Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive di... more BACKGROUND Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive disease in the mitochondrial transport of long-chain fatty acids. Despite early diagnosis and treatment, the disease still has a high mortality rate. METHODS Clinical symptoms, long-term follow-up, and biochemical and molecular results of four cases are described and compared with the reviewed literature data of 55 cases. RESULTS Two cases with neonatal onset, carrying in homozygosity the novel variant sequences p.Gly20Asp (c.59G>A) and p.Arg179Gly (c.536A>G), died during an intercurrent infectious process in the first year of life despite adequate dietetic treatment (frequent feeding, high-carbohydrate/low-fat diet, MCT, carnitine). The other two cases, one with infantile onset and the other diagnosed in the newborn period after a previous affected sibling, show excellent development at 4 and 16 years of age under treatment. The review shows that the most frequent presenting symptom...
Resumen Los tres factores principales implicados en la caries son las bacterias, los azúcares y l... more Resumen Los tres factores principales implicados en la caries son las bacterias, los azúcares y la susceptibilidad del huésped, mientras que los procedimientos más útiles como profilácticos de la misma son el empleo de flúor, las medidas dietéticas, la higiene dental y el tratamiento de las lesiones activas. El flúor más efectivo para la prevención de la caries es el tópico administrado de forma continua. Este dato, junto con el conocimiento de que el exceso de flúor sistémico en la fase preeruptiva se asocia con la fluorosis dental hace que el cepillado dental con una pasta que contenga flúor es actualmente la medida más recomendable para la prevención de la caries. Es más importante la minuciosidad del cepillado dental que el tipo de técnica empleada. Solamente se recomiendan suplementos de fluoruro si se pertenece a un grupo de riesgo de caries dental y la cantidad que debe administrarse está en función de la concentración de ion flúor del agua de consumo, ya que los alimentos no constituyen una fuente importante de flúor. Los colutorios de fluoruro que se emplean para realizar enjuagues bucales diarios o semanales, deben recomendarse a partir de los seis años para asegurar que el niño no ingerirá el líquido. La cariogenicidad de los azúcares depende más del tipo de hidrato de carbono y del tiempo de retención bucal que de la cantidad consumida, por lo que se desaconseja especialmente la ingesta de biberones durante el sueño.
Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by mutations in th... more Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. Skeletal dysplasia and the related clinical features of MPS IVA are caused by disruption of the cartilage and its extracellular matrix, leading to a growth imbalance. Enzyme replacement therapy (ERT) with recombinant human GALNS has yielded positive results in activity of daily living and endurance tests. However, no data have demonstrated improvements in bone lesions and bone grow thin MPS IVA after ERT, and there is no correlation between therapeutic efficacy and urine levels of keratan sulfate, which accumulates in MPS IVA patients. Using qualitative and quantitative proteomics approaches, we analyzed leukocyte samples from healthy controls (n = 6) and from untreated (n = 5) and ERT-treated (n = 8, sampled before and after treatment) MPS IVA patients to identify potential biomarkers of disease. Out of 690 proteins identified in leukocy...
Congenital lactic acidosis (CLA) is a rare condition in most instances due to a range of inborn e... more Congenital lactic acidosis (CLA) is a rare condition in most instances due to a range of inborn errors of metabolism that result in defective mitochondrial function. Even though the implementation of next generation sequencing has been rapid, the diagnosis rate for this highly heterogeneous allelic condition remains low. The present work reports our group’s experience of using a clinical/biochemical analysis system in conjunction with genetic findings that facilitates the taking of timely clinical decisions with minimum need for invasive procedures. The system’s workflow combines different metabolomics datasets and phenotypic information with the results of clinical exome sequencing and/or RNA analysis. The system’s use detected genetic variants in 64% of a cohort of 39 CLA-patients; these variants, 14 of which were novel, were found in 19 different nuclear and two mitochondrial genes. For patients with variants of unknown significance, the genetic analysis was combined with functio...
Background: In patients with phenylketonuria (PKU), a low-phenylalanine (Phe) diet supplemented w... more Background: In patients with phenylketonuria (PKU), a low-phenylalanine (Phe) diet supplemented with lowprotein foods and a Phe-free amino acid mixture favors a dietary intake rich in carbohydrates, but little is known about how these molecules are metabolized in this setting. The objective of the present study was to analyze carbohydrate metabolism in patients with hyperphenylalaninemia. Methods: We conducted a multicenter cross-sectional study to investigate biochemical markers of basal and postprandial carbohydrate metabolism in PKU patients according to age, Phe tolerance, waist circumference and body mass index (BMI), diet, tetrahydrobiopterin (BH4) supplementation, and adherence to treatment. Basal biomarkers and anthropometric parameters were also evaluated in patients with mild hyperphenylalaninemia (MHPA) and in healthy controls. Results: A total of 83 patients aged 4-52 years were studied; 68.7% had PKU and 31.3% had MHPA. 68 healthy controls of similar sex and age were also evaluated Metabolic control was adequate in 71.9% of PKU patients. Fasting glucose levels (mean 80.77 ± 8.06 mg/dL) were high in just one patient, but fasting insulin levels, with a mean of 12.74 ± 8.4 mIU/L, were altered in 15 PKU patients (26.3%) and markedly higher than in patients with MPHA (p = 0.035). Fasting insulin levels and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) were significantly higher than in healthy controls and correlated with body mass index, waist circumference, age, and also showed statistically significant differences according to diagnosis and Phe tolerance (p < 0.05). Patients under BH4 therapy had lower insulin levels and HOMA-IR. A higher mean carbohydrate intake from AA mixtures was observed in classic PKU patients. The caloric intake in the form of carbohydrates was also higher in PKU than MHPA patients (p = 0.038) and it was correlated with basal insulin (rho = 0.468, p = 0.006), HOMA-IR (rho = 0.423, p = 0.02), BMI (rho 0.533, p = 0.002), and waist circumference (rho 0.584, p = 0.0007). Conclusions: This study shows that PKU patients are at risk of carbohydrate intolerance and insulin resistance, more evident in adults and overweight patients, probably related to their higher caloric intake in form carbohydrate content. A higher dependency of AA mixtures was demonstrated in PKU patients.
The present work describes the value of genetic analysis as a confirmatory measure following the ... more The present work describes the value of genetic analysis as a confirmatory measure following the detection of suspected inborn errors of metabolism in the Spanish newborn mass spectrometry screening program. One hundred and forty-one consecutive DNA samples were analyzed by next-generation sequencing using a customized exome sequencing panel. When required, the Illumina extended clinical exome panel was used, as was Sanger sequencing or transcriptional profiling. Biochemical tests were used to confirm the results of the genetic analysis. Using the customized panel, the metabolic disease suspected in 83 newborns (59%) was confirmed. In three further cases, two monoallelic variants were detected for two genes involved in the same biochemical pathway. In the remainder, either a single variant or no variant was identified. Given the persistent absence of biochemical alterations, carrier status was assigned in 39 cases. False positives were recorded for 11. In five cases in which the biochemical pattern was persistently altered, further genetic analysis allowed the detection of two variants affecting the function of BCAT2, ACSF3, and DNAJC12, as well as a second, deep intronic variant in ETFDH or PTS. The present results suggest that genetic analysis using extended next-generation sequencing panels can be used as a confirmatory test for suspected inborn errors of metabolism detected in newborn screening programs. Biochemical tests can be very helpful when a diagnosis is unclear. In summary, simultaneous genomic and metabolomic analyses can increase the number of inborn errors of metabolism that can be confirmed following suggestive newborn screening results.
Importancia del agua mineral natural como aporte de nutrientes esenciales Natural mineral water. ... more Importancia del agua mineral natural como aporte de nutrientes esenciales Natural mineral water. Essential nutrients Maraver F (1-2) , Vitoria I (3) , Morer C (4-2) , Armijo F (1-2)
International Journal of Food Science, Nutrition and Dietetics, 2015
Fluoride has multiple mechanisms of action [5]. First, the hydroxyapatite crystals in the enamel ... more Fluoride has multiple mechanisms of action [5]. First, the hydroxyapatite crystals in the enamel become fluorapatite crystals, which are more resistant to decalcification. This chemical reaction is reversible and depends on the concentration of fluoride and acidity in the environment of the tooth enamel. Thus, the hydroxyapatite crystal begins to dissolve when the pH is less than 5.5, whereas fluorapatite dissolves when the pH is less than 4.5
Natural sources of protein and some vitamins and minerals are limited in phenylketonuria (PKU) tr... more Natural sources of protein and some vitamins and minerals are limited in phenylketonuria (PKU) treated patients, who should receive optimal supplementation although this is not yet fully established. We conducted a cross-sectional observational multicenter study including 156 patients with hyperphenylalaninemia. Patients were stratified by age, phenotype, disease detection and type of treatment. Annual median blood phenylalanine (Phe) levels, Phe tolerance, anthropometric measurements, and biochemical parameters (total protein, prealbumin, electrolytes, selenium, zinc, B12, folic acid, ferritin, 25-OH vitamin D) were collected in all patients. 81.4% of patients had biochemical markers out of recommended range but no clinical symptoms. Total protein, calcium, phosphorus, B12, ferritin, and zinc levels were normal in most patients. Prealbumin was reduced in 34.6% of patients (74% with PKU phenotype and 94% below 18years old), showing almost all (96.3%) an adequate adherence to diet. Selenium was diminished in 25% of patients (95% with PKU phenotype) and also 25-OHD in 14%. Surprisingly, folic acid levels were increased in 39% of patients, 66% with classic PKU. Phosphorus and B12 levels were found diminished in patients with low adherence to diet. Patients under BH4 therapy only showed significant lower levels of B12. This study shows a high percentage of prealbumin and selenium deficiencies as well as an increased level of folic acid in PKU treated patients, which should lead us to assess an adjustment for standards supplements formulated milks.
Despite a strict dietary control, patient with hyperphenylalaninemia or phenylketonuria may show ... more Despite a strict dietary control, patient with hyperphenylalaninemia or phenylketonuria may show cognitive and/or behavioral disorders. These comorbid deficits are of great concern to patients, families, and health organizations. However, biomarkers capable of detecting initial stages of neurological damage are not commonly employed. The pathogenesis of phenylketonuria is complex in nature. Increasingly, the role of oxidative stress has gained acceptance and biomarkers reflecting oxidative damage to the brain and easily accessible in peripheral biofluids have been validated using mass spectrometry techniques. In the present review, the role of oxidative stress in the pathogenesis of phenylketonuria and hyperphenylalaninemia has been updated. Moreover, we report on newly validated brain-specific lipid peroxidation biomarkers and inform on their relevance in the detection and monitoring of neurological damage in phenylketonuric patients. In preliminary studies, a correlation between lipid peroxidation biomarkers and neurological dysfunction in patients with PKU was reported. However, there is a need of adequately powered trials to confirm the validity of these biomarkers for early detection of brain damage, initiation of treatment, and reliably monitor evolving disease both in phenylketonuria and hyperphenylalaninemia.
Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providin... more Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providing sufficient energy to avoid catabolism and to limit production of methylmalonic acid. The goal is to achieve normal growth, good nutritional status and the maintenance of metabolic stability. Aim To describe the dietary management of patients with MMA across Europe. Methods A cross-sectional questionnaire was sent to European colleagues managing inherited metabolic disorders (IMDs) (n=53) with 27 questions about the nutritional management of organic acidaemias. Data were analysed by different age ranges (0–6 months; 7–12 months; 1–10 years; 11–16 years; >16 years). Results Questionnaires were returned from 53 centres. Twenty-five centres cared for 80 patients with MMA vitamin B12 responsive (MMAB12r) and 43 centres managed 215 patients with MMA vitamin B12 non-responsive (MMAB12nr). For MMAB12r patients, 44% of centres (n=11/25) prescribed natural protein below the World Health Organ...
Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affect... more Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. Methods: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. Results: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m 2. The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-Lhomocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. Conclusions: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients.
Se ha revisado la composición de 164 bebidas vegetales disponibles en España a partir del etiquet... more Se ha revisado la composición de 164 bebidas vegetales disponibles en España a partir del etiquetado nutricional del envase y de las páginas web de los fabricantes. Se ha comparado con la composición de la leche de vaca y de la fórmula infantil. Además, se ha revisado la patología nutricional asociada con el consumo de bebidas vegetales en lactantes y niños mediante una búsqueda bibliográfica en Medline y EMBASE desde 1990 basada en las palabras clave “plant-based beverages” o “rice beverages” o “almond beverages” o “soy beverages” y “infant” o “child”.
INTRODUCTION: An appropriate magnesium intake has proved to have beneficial effects on bone healt... more INTRODUCTION: An appropriate magnesium intake has proved to have beneficial effects on bone health, reduce insulin resistance and prevent atherosclerosis. Our objective was to determine the concentration of magnesium in bottled mineral water in Spain and assess its daily contribution to dietary recommendations.MATERIAL-METHODS: We used ion chromatography to analyse the magnesium concentrations of 97 spanish natural mineral waters.RESULTS - CONCLUSIONS: The average magnesium concentration of 97 brands of Spanish natural mineral water was 16.2 mg/L (range: 0.1-141.2 mg/L). Of these, 33 contained between 15 and 45 mg/L of magnesium and four contained over 45 mg/L.Assuming water consumption is as recommended by the European Food Safety Agency, water containing 15 to 45 mg/L of magnesium provides between 9 and 76.5% of the recommended intake of magnesium for children aged one to thirteen, up to 25.7% in adolescents, between 7.5 and 25.7% for adults, and up to 27% for lactating women. Wat...
BACKGROUND Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive di... more BACKGROUND Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive disease in the mitochondrial transport of long-chain fatty acids. Despite early diagnosis and treatment, the disease still has a high mortality rate. METHODS Clinical symptoms, long-term follow-up, and biochemical and molecular results of four cases are described and compared with the reviewed literature data of 55 cases. RESULTS Two cases with neonatal onset, carrying in homozygosity the novel variant sequences p.Gly20Asp (c.59G>A) and p.Arg179Gly (c.536A>G), died during an intercurrent infectious process in the first year of life despite adequate dietetic treatment (frequent feeding, high-carbohydrate/low-fat diet, MCT, carnitine). The other two cases, one with infantile onset and the other diagnosed in the newborn period after a previous affected sibling, show excellent development at 4 and 16 years of age under treatment. The review shows that the most frequent presenting symptom...
Resumen Los tres factores principales implicados en la caries son las bacterias, los azúcares y l... more Resumen Los tres factores principales implicados en la caries son las bacterias, los azúcares y la susceptibilidad del huésped, mientras que los procedimientos más útiles como profilácticos de la misma son el empleo de flúor, las medidas dietéticas, la higiene dental y el tratamiento de las lesiones activas. El flúor más efectivo para la prevención de la caries es el tópico administrado de forma continua. Este dato, junto con el conocimiento de que el exceso de flúor sistémico en la fase preeruptiva se asocia con la fluorosis dental hace que el cepillado dental con una pasta que contenga flúor es actualmente la medida más recomendable para la prevención de la caries. Es más importante la minuciosidad del cepillado dental que el tipo de técnica empleada. Solamente se recomiendan suplementos de fluoruro si se pertenece a un grupo de riesgo de caries dental y la cantidad que debe administrarse está en función de la concentración de ion flúor del agua de consumo, ya que los alimentos no constituyen una fuente importante de flúor. Los colutorios de fluoruro que se emplean para realizar enjuagues bucales diarios o semanales, deben recomendarse a partir de los seis años para asegurar que el niño no ingerirá el líquido. La cariogenicidad de los azúcares depende más del tipo de hidrato de carbono y del tiempo de retención bucal que de la cantidad consumida, por lo que se desaconseja especialmente la ingesta de biberones durante el sueño.
Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by mutations in th... more Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. Skeletal dysplasia and the related clinical features of MPS IVA are caused by disruption of the cartilage and its extracellular matrix, leading to a growth imbalance. Enzyme replacement therapy (ERT) with recombinant human GALNS has yielded positive results in activity of daily living and endurance tests. However, no data have demonstrated improvements in bone lesions and bone grow thin MPS IVA after ERT, and there is no correlation between therapeutic efficacy and urine levels of keratan sulfate, which accumulates in MPS IVA patients. Using qualitative and quantitative proteomics approaches, we analyzed leukocyte samples from healthy controls (n = 6) and from untreated (n = 5) and ERT-treated (n = 8, sampled before and after treatment) MPS IVA patients to identify potential biomarkers of disease. Out of 690 proteins identified in leukocy...
Congenital lactic acidosis (CLA) is a rare condition in most instances due to a range of inborn e... more Congenital lactic acidosis (CLA) is a rare condition in most instances due to a range of inborn errors of metabolism that result in defective mitochondrial function. Even though the implementation of next generation sequencing has been rapid, the diagnosis rate for this highly heterogeneous allelic condition remains low. The present work reports our group’s experience of using a clinical/biochemical analysis system in conjunction with genetic findings that facilitates the taking of timely clinical decisions with minimum need for invasive procedures. The system’s workflow combines different metabolomics datasets and phenotypic information with the results of clinical exome sequencing and/or RNA analysis. The system’s use detected genetic variants in 64% of a cohort of 39 CLA-patients; these variants, 14 of which were novel, were found in 19 different nuclear and two mitochondrial genes. For patients with variants of unknown significance, the genetic analysis was combined with functio...
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