RESUMEN
The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case-control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score -0.12 (1.06) vs. -0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.
Asunto(s)
Enfermedad Celíaca , Niño , Humanos , Enfermedad Celíaca/diagnóstico , Estudios de Casos y Controles , Transglutaminasas , Tamizaje Masivo , Inmunoglobulina A , AutoanticuerposRESUMEN
Celiac disease is strongly associated with HLA DQ, specifically with haplotypes. DRB1*03-DQA1*05:01/DQB1*02:01 (DQ2.5),DRB1*07-DQA1*02:01/DQB1*02:02 (DQ2.2), DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), and DRB1*04-DQA1*03:01/DQB1*03:02 (DQ8). The distribution of these risk haplotypes in patients with celiac disease is different in the geographical areas investigated. A high frequency of DRB1*07- DQA1*02:01/DQB1*02:02 (DQ2.2) and DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), has been described in Southern Europe. We analyzed 2102 confirmed CD cases with information on both DQB1* alelles and their distribution by geographical area in Spain. According to the presence of this haplotype in one or two chromosomes, the genotype is classified in: DQ2 homozygous, DQ2 heterozygous (cis or trans), DQ8 homozygous, DQ8/DQ2.5, DQ 2.2 homozygous and genotype known as "half DQ2". Two different patterns of risks related to CD were identified. In the Basque Country and Navarre, the Mediterranean Area (Aragon, Catalonia, Valencia, Balearic Islands, and Murcia), the South of Spain (Andalucía and Extremadura), and the Canary Islands, higher frequency of DQ2.5 trans, and more than 80% of DQ2.5/DQ2.2 homozygosis were described. The Cantabrian Coast (Cantabria, Asturias, and Galicia) and Central Areas (Castilla-León and Castilla-La Mancha) showed a higher percentage of DQ2.5/DQ2.5 homozygosis and a lower DQ2.5 in trans frequency, as in Northern Europe. Madrid has an intermediate model between the two described above. 17 cases (0.8%) did not carry any CD risk haplotypes.
Asunto(s)
Enfermedad Celíaca , Antígenos HLA-DQ , Humanos , Niño , España/epidemiología , Antígenos HLA-DQ/genética , Enfermedad Celíaca/genética , Predisposición Genética a la Enfermedad , Alelos , Genotipo , Haplotipos , Cadenas beta de HLA-DQ/genética , Cadenas alfa de HLA-DQ/genéticaRESUMEN
OBJECTIVES: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD). METHODS: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed. RESULTS: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms. CONCLUSIONS: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels.
Asunto(s)
Enfermedad Celíaca , Adolescente , Niño , Humanos , Autoanticuerpos , Biopsia , Enfermedad Celíaca/diagnóstico , Inmunoglobulina A , Inmunoglobulina G , TransglutaminasasRESUMEN
BACKGROUND: The early detection and management of children with metabolic associated fatty liver disease (MAFLD) is challenging. OBJECTIVE: To develop a non-invasive and accurate prediction protocol for the identification of MAFLD among children with overweight/obesity candidates to confirmatory diagnosis. METHODS: A total of 115 children aged 8-12 years with overweight/obesity, recruited at a primary care, were enrolled in this cross-sectional study. The external validation was performed using a cohort of children with overweight/obesity (N = 46) aged 8.5-14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic resonance imaging (MRI). Fasting blood biochemical parameters were measured, and 25 candidates' single nucleotide polymorphisms (SNPs) were determined. Variables potentially associated with the presence of MAFLD were included in a multivariate logistic regression. RESULTS: Children with MAFLD (36%) showed higher plasma triglycerides (TG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyl-transferase (GGT) and ferritin (p < 0.05). The distribution of the risk-alleles of PPARGrs13081389, PPARGrs1801282, HFErs1800562 and PNLPLA3rs4823173 was significantly different between children with and without MAFLD (p < 0.05). Three biochemical- and/or SNPs-based predictive models were developed, showing strong discriminatory capacity (AUC-ROC: 0.708-0.888) but limited diagnostic performance (sensitivity 67%-82% and specificity 63%-69%). A prediction protocol with elevated sensitivity (72%) and specificity (84%) based on two consecutive steps was developed. The external validation showed similar results: sensitivity of 70% and specificity of 85%. CONCLUSIONS: The HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Sobrepeso , Obesidad Infantil , Alanina Transaminasa , Aspartato Aminotransferasas , Niño , Estudios Transversales , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Sobrepeso/complicaciones , Obesidad Infantil/complicacionesRESUMEN
BACKGROUND: Hepatic steatosis (HS) is currently the most prevalent hepatic disease in paediatric population and a major risk factor for type 2 diabetes and cardiovascular diseases. The proper identification of children with HS is therefore of great public health interest. OBJECTIVE: To develop a new prediction score using anthropometric, sociodemographic and lifestyle factors to identify children with HS (the HEPAKID index). Previously published biochemical paediatric screening tools were validated in the same cohort. METHODS: A total of 115 pre-adolescent children aged 8 to 12 years with overweight/obesity, recruited at hospital paediatric units were enrolled in this cross-sectional study. HS (≥5.5% hepatic fat) was assessed by magnetic resonance imaging (MRI). Anthropometric, sociodemographic and lifestyle variables were collected by validated tests/questionnaires. RESULTS: Forty-one children had MRI-diagnosed HS (35.6%, 49% girls). These children had (P < .01) a higher waist-height ratio, a lower cardiorespiratory fitness, a younger gestational age, and consumed more sugar-sweetened beverages than their HS-free peers. Children with HS were more likely to belong to an ethnic minority (P < .01) and to spend longer viewing screens than recommended (P < .05). The addition of these variables to the multivariate logistic regression model afforded a HEPAKID index with high discriminatory capacity (area under the receiver-operating characteristic curve: 0.808, 95% CI 0.715-0.901), and score of ≥25.0 was associated with high sensitivity (82%, 95% CI 68%-96%). Biochemical biomarker-based paediatric tools for identifying HS showed only moderate discriminatory capacity and low sensitivity (5%-41%) in this cohort. CONCLUSIONS: The HEPAKID index is the first simple, non-invasive, sensitive, inexpensive and easy-to-perform screening that can identify children with overweight or obesity who have HS.
Asunto(s)
Hígado Graso , Tamizaje Masivo , Obesidad Infantil , Antropometría , Niño , Estudios Transversales , Demografía , Hígado Graso/diagnóstico , Femenino , Humanos , Estilo de Vida , Masculino , Tamizaje Masivo/métodos , Obesidad Infantil/epidemiología , Factores de Riesgo , Factores SociológicosRESUMEN
Coeliac disease is a systemic immune-mediated disorder triggered by the ingestion of gluten, which is given in genetically predisposed subjects. It manifests with a wide variety of clinical symptoms, specific serological markers, HLA-DQ2/DQ8 haplotype and enteropathy. The criteria followed for this have usually been those established by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) since 1969. These criteria have advanced from the need of several intestinal biopsies to, thanks to the development of serological tests of high sensitivity and specificity, considering the enteropathy as one more element in this diagnosis and makes it possible to perform a diagnosis without the need of an intestinal biopsy in certain circumstances. The updated review of the 2012 criteria in 2019 provides new evidence on some aspects, such as the role of HLA, the diagnosis of asymptomatic patients, and the effectiveness of the serological markers. These aspects are reviewed in detail, with the aim of facilitating the rational application of the new 2020 criteria at all care levels. In this sense, Paediatric Primary Care is fundamental in the search for active cases and to perform a first serological study, being recommended that the diagnosis is always established by a Paediatric Gastroenterologist.
Asunto(s)
Enfermedad Celíaca/diagnóstico , Antígenos HLA-DQ/genética , Enfermedad Celíaca/genética , Niño , Gastroenterología , Glútenes/efectos adversos , Humanos , Sensibilidad y EspecificidadRESUMEN
Treatment with nitisinone (NTBC) has brought about a drastic improvement in the treatment and prognosis of hereditary tyrosinemia type I (HT1). We conducted a retrospective observational multicentric study in Spanish HT1 patients treated with NTBC to assess clinical and biochemical long-term evolution.We evaluated 52 patients, 7 adults and 45 children, treated with NTBC considering: age at diagnosis, diagnosis by clinical symptoms, or by newborn screening (NBS); phenotype (acute/subacute/chronic), mutational analysis; symptoms at diagnosis and clinical course; biochemical markers; doses of NTBC; treatment adherence; anthropometric evolution; and neurocognitive outcome.The average follow-up period was 6.1â±â4.9 and 10.6â±â5.4 years in patients with early and late diagnosis respectively. All patients received NTBC from diagnosis with an average dose of 0.82âmg/kg/d. All NBS-patients (nâ=â8) were asymptomatic at diagnosis except 1 case with acute liver failure, and all remain free of liver and renal disease in follow-up. Liver and renal affectation was markedly more frequent at diagnosis in patients with late diagnosis (Pâ<â.001 and .03, respectively), with ulterior positive hepatic and renal course in 86.4% and 93.2% of no-NBS patients, although 1 patient with good metabolic control developed hepatocarcinoma.Despite a satisfactory global nutritional evolution, 46.1% of patients showed overweight/obesity. Interestingly lower body mass index was observed in patients with good dietary adherence (20.40â±â4.43 vs 24.30â±â6.10; Pâ=â.08) and those with good pharmacological adherence (21.19â±â4.68 vs 28.58â±â213.79).intellectual quotient was ≥85 in all NBS- and 68.75% of late diagnosis cases evaluated, 15% of which need pedagogical support, and 6.8% (3/44) showed school failure.Among the 12 variants identified in fumarylacetoacetate hydrolase gene, 1 of them novel (H63D), the most prevalent in Spanish population is c.554-1 G>T.After NTBC treatment a reduction in tyrosine and alpha-fetoprotein levels was observed in all the study groups, significant for alpha-fetoprotein in no NBS-group (Pâ=â.03), especially in subacute/chronic forms (Pâ=â.018).This series confirms that NTBC treatment had clearly improved the prognosis and quality of life of HT1 patients, but it also shows frequent cognitive dysfunctions and learning difficulties in medium-term follow-up, and, in a novel way, a high percentage of overweight/obesity.
Asunto(s)
Ciclohexanonas/uso terapéutico , Diagnóstico Tardío , Nitrobenzoatos/uso terapéutico , Obesidad , Calidad de Vida , Tirosinemias , Adulto , Niño , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Diagnóstico Tardío/efectos adversos , Diagnóstico Tardío/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Masculino , Evaluación de Necesidades , Tamizaje Neonatal/métodos , Obesidad/diagnóstico , Obesidad/etiología , Pronóstico , Estudios Retrospectivos , España , Tiempo de Tratamiento , Tirosinemias/complicaciones , Tirosinemias/diagnóstico , Tirosinemias/tratamiento farmacológico , Tirosinemias/psicologíaRESUMEN
INTRODUCTION: Cow's milk allergy (CMA) is a common diagnosis in infants, requiring the exclusion of cow's milk until tolerance is recovered. In the present study, we aim to determine which factors are associated with the development of tolerance. METHODS: Retrospective, observational study of subjects who underwent the same clinical follow-up methodology. We studied 245 cases of CMA (125 IgE-mediated and 120 non-IgE-mediated). The following variables were analysed: age at diagnosis, gender, type of delivery, type of feeding received, feeding during the first months of life, clinical features, and type of feed received as treatment: casein hydrolysates or casein hydrolysates with Lactobacillus rhamnosus GG (LGG). RESULTS: Factors associated with earlier tolerance were non-IgE-mediated CMA (HR = 2.92; 95% CI: 2.20-3.88) and patients receiving casein hydrolysate with LGG (HR = 1.79; 95% CI: 1.33-2.42). Later tolerance was associated with caesarean delivery (HR = 0.78; 95% CI: 0.58-1.05) and breastfeeding for a period of at least 3 days (HR = 0.64; 95% CI: 0.44-0.93). The multivariate study shows that the type of formula (HR = 1.61; 95% CI: 1.19-2.18) and the type of CMA (HR = 2.82; 95% CI: 2.12-3.85) have an effect on the recovery time. Casein hydrolysates with LGG reduces the recovery time in IgE-mediated (HR = 1.88; 95% CI: 1.17-3.01) and non-IgE-mediated CMA (HR = 1.46; 95% CI: 0.98-2.17). CONCLUSIONS: Tolerance acquisition is faster in non-IgE-mediated CMA subjects and in those who received casein hydrolysate with LGG.
Asunto(s)
Tolerancia Inmunológica , Hipersensibilidad a la Leche/epidemiología , Alérgenos/inmunología , Animales , Caseínas/uso terapéutico , Bovinos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina E/metabolismo , Masculino , Hipersensibilidad a la Leche/dietoterapia , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/inmunología , Estudios Retrospectivos , Factores de Riesgo , España/epidemiologíaRESUMEN
Background: Cow milk allergy (CMA) is the most common food allergy in infants. Some patients will express, in the future, other allergic diseases (allergic march). Objective: To evaluate if a new scoring system could determine the risk of developing allergic march. Methods: A retrospective observational cohort study of subjects who were immunoglobulin E (IgE) mediated was conducted. We defined a risk score for atopy (RSA), including clinical and laboratory variables. Three risk groups were defined according to the RSA. We defined as dependent variables atopy (one or more allergic diseases) and atopy+ (two or more allergic diseases). A multivariate logistic regression model was created, which included RSA and the type of formula (high-grade extended hydrolyzed formula [EHF] with Lactobacillus rhamnosus GG (LGG), high-grade EHF without LGG, and other formulas). Results: A total of 211 patients were recruited. When we analyzed the risk of atopy+, we found an increased risk for RSA intermediate-risk (odds ratio [OR 2.08] [95% confidence interval {CI}, 0.95-4.56) and high-risk (OR 24.74 [95% CI, 6.26-97.73]) groups, and a decreased risk for the subjects fed with high-grade EHF (OR 0.42 [95% CI, 0.20-0.87]) and also in those subjects fed with high-grade EHF plus LGG (OR 0.30 [95% CI, 0.09-0.98]). Conclusion: RSA is a simple and useful tool to predict the risk of developing other allergic diseases in patients with IgE-mediated CMA.
Asunto(s)
Alérgenos/inmunología , Inmunoglobulina E/inmunología , Hipersensibilidad a la Leche/inmunología , Leche/efectos adversos , Adolescente , Animales , Bovinos , Niño , Femenino , Humanos , Hidrólisis , Inmunoglobulina E/sangre , Masculino , Hipersensibilidad a la Leche/diagnóstico , Probióticos , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Adulto JovenAsunto(s)
Anafilaxia/diagnóstico , Condroitinsulfatasas/efectos adversos , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/diagnóstico , Terapia de Reemplazo Enzimático/efectos adversos , Reacción en el Punto de Inyección/diagnóstico , Omalizumab/uso terapéutico , Alérgenos/inmunología , Prueba de Desgranulación de los Basófilos , Preescolar , Condroitinsulfatasas/inmunología , Condroitinsulfatasas/uso terapéutico , Humanos , Tolerancia Inmunológica , Inmunoglobulina E/metabolismo , Masculino , Mucopolisacaridosis IV , Pruebas Cutáneas , UrticariaRESUMEN
INTRODUCTION: the recent economic and financial crisis has affected most Western countries, especially families of low socioeconomic classes. We speculate that worsening of socioeconomic condition associated with the crisis would increase obesity, mainly in disadvantaged families. MATERIAL AND METHODS: cross-sectional study of the 290,111 children aged three to 12 years old attending public school during the term 2014-2015 in Madrid City, by means of a stratified weighted sample randomly chosen, taking into account age (grade), city district and schools. The questionnaire included weight and height (auto-reported), dietary report (weekly frequency of intake), as well as socioeconomic variables. RESULTS: 1,208 questionnaires were evaluated from 64 classes. Half of participants were boys; 42% were younger than five years old, 35% werebetween six and eight years old, and 23% older than eight. Undernutrition was present in 5.0%, and excess of weight (overweight + obesity) in 36.7%. Undernutrition was higher in children under the age of six (9.1%). No relationship was found between undernutrition and the characteristics of the families but was slightly higher in families where both parents were unemployed. Excess of weight was higher in children of non-Spaniard parents (44% vs 32%, p < 0.0001), as well as in those families with economic problems (41% vs 31%, p = 0.0005). Only for meat, grains and dairy, the weekly intake was close to the recommendations. CONCLUSIONS: children from lower income households were at a higher risk of being overweight compared with their peers. Participation in a school-based food aid program may reduce food insecurity for children and their families.
Asunto(s)
Recesión Económica/estadística & datos numéricos , Conducta Alimentaria/psicología , Estado Nutricional , Niño , Fenómenos Fisiológicos Nutricionales Infantiles , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Obesidad/epidemiología , Sobrepeso/epidemiología , Pobreza , España/epidemiología , Encuestas y Cuestionarios , Población UrbanaRESUMEN
Coeliac disease (CD) is a chronic autoimmune enteropathy triggered by gluten and related prolamines in genetically predisposed individuals. Although CD is a polygenic disease, there is a strong association with genes of the human leukocyte antigen (HLA) region. Most patients present the HLA-DQ2 heterodimer, specifically the DQ2.5 isoform, which is present in around 90-96% of patients of European ancestry.
Asunto(s)
Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/genética , Antígenos HLA/genética , Predisposición Genética a la Enfermedad , HumanosRESUMEN
BACKGROUND: Cow milk allergy (CMA) is the most common food allergy in breastfed infants. The aim of this study is to verify whether certain perinatal factors may influence the development of CMA immunoglobulin E (IgE)+. METHODS: A retrospective, observational study of case and control groups was carried out. Information was collected of patients with CMA IgE+ from our department during the years 1990-2013. Patients of the same age and sex were recruited for the control group. Information on the following variables was collected: sex, age, pregnancy tolerance, duration of pregnancy, type of delivery, isolated doses of formula feeding in hospital (FFH), duration of breastfeeding, and family history of allergy (defined as ≥1 first-degree family member with allergic disease). Statistical analysis was performed using multivariate logistic regression techniques. RESULTS: A total of 211 cases were included in this study. Multivariate analysis showed an influence of duration of breastfeeding, FFH to be a risk factor (OR 4.94; 95% CI 2.68-9.08), especially in caesarean delivery (OR 11.82; 95% CI 2.64-47.50), and prematurity (OR 0.29; 95% CI 0.09-0.92) to be a protective factor. CONCLUSIONS: Perinatal factors play a key role in the development of CMA IgE+, with an influence of breastfeeding duration, FFH and caesarean delivery as risk factors and prematurity as a protective factor. While family history had no important role, environmental factors were more decisive.
Asunto(s)
Fórmulas Infantiles/estadística & datos numéricos , Hipersensibilidad a la Leche/epidemiología , Adolescente , Adulto , Lactancia Materna , Cesárea , Niño , Femenino , Humanos , Inmunoglobulina E/inmunología , Lactante , Masculino , Hipersensibilidad a la Leche/inmunología , Embarazo , Estudios Retrospectivos , Factores de Riesgo , España , Adulto JovenRESUMEN
The mucopolysaccharidoses (MPSs) are underdiagnosed but they are evaluated in few newborn screening programs, probably due to the many challenges remaining, such as the identification of late-onset phenotypes. Systematic screening at the onset of clinical symptoms could help to early identify patients who may benefit from specific treatments. The aim of this prospective study was to assess a novel selective screening program, the FIND project, targeting patients aged 0 to 16 years with clinical manifestations of MPS. The project was designed to increase awareness of these diseases among pediatricians and allow early diagnosis.From July 2014 to June 2016, glycosaminoglycan (GAG) levels normalized to creatinine levels were determined in urine-impregnated analytical paper submitted by pediatricians who had patients with clinical signs and/or symptoms compatible with MPS. When high GAG concentrations were detected, a new liquid urine sample was requested to confirm and identify the GAG present. When a specific form of MPS was suspected, enzyme activity was analyzed using blood-impregnated paper to determine MPS type (I, IIIB, IIIC, IVA, IVB, VI, or VII). Age-specific reference values for GAG were previously established using 145 urine samples from healthy children.GAG levels were normal in 147 (81.7%) of the 180 initial samples received. A liquid sample was requested for the other 33 cases (18.3%); GAG levels were normal in 13 of these and slightly elevated in 12, although the electrophoresis study showed no evidence of MPS. Elevated levels with corresponding low enzymatic activity were confirmed in 8 cases. The mean time from onset of clinical symptoms to detection of MPS was 22 months, and just 2 cases were detected at the beginning of the project were detected with 35 and 71 months of evolution of clinical symptoms. Our screening strategy for MPS had a sensitivity of 100%, a specificity of 85%, and a positive predictive value of 24%.The FIND project is a useful and cost-effective screening method for increasing awareness of MPS among pediatricians and enabling the detection of MPS at onset of clinical symptoms.
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Tamizaje Masivo , Mucopolisacaridosis/diagnóstico , Adolescente , Biomarcadores/orina , Niño , Preescolar , Diagnóstico Precoz , Femenino , Fluorometría , Estudios de Seguimiento , Glicosaminoglicanos/orina , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lactante , Recién Nacido , Masculino , Mucopolisacaridosis/enzimología , Mucopolisacaridosis/genética , Mucopolisacaridosis/orina , Pediatras , Estudios Prospectivos , Sensibilidad y Especificidad , EspañaRESUMEN
Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.
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Estudios de Asociación Genética , Genotipo , Mutación , Fenotipo , Fenilalanina Hidroxilasa/genética , Fenilcetonurias/epidemiología , Fenilcetonurias/genética , Alelos , Terapia de Reemplazo Enzimático , Frecuencia de los Genes , Heterogeneidad Genética , Humanos , Epidemiología Molecular , Fenilalanina Hidroxilasa/metabolismo , Fenilcetonurias/diagnóstico , Fenilcetonurias/terapia , España/epidemiologíaRESUMEN
OBJECTIVES: A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD). METHODS: The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy. RESULTS: CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse. CONCLUSIONS: Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.
Asunto(s)
Anticuerpos/metabolismo , Enfermedad Celíaca/diagnóstico , Dieta , Glútenes/inmunología , Antígenos HLA/genética , Intestino Delgado/patología , Adolescente , Biopsia , Enfermedad Celíaca/genética , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/patología , Niño , Preescolar , Humanos , Lactante , Intestino Delgado/metabolismo , Guías de Práctica Clínica como Asunto , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Sociedades Médicas , EspañaRESUMEN
BACKGROUND AND AIMS: Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life. METHODS: We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome. RESULTS: No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration. CONCLUSIONS: Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes.
Asunto(s)
Biopterinas/análogos & derivados , Estatura , Peso Corporal , Estado Nutricional , Fenilcetonurias/tratamiento farmacológico , Biopterinas/administración & dosificación , Biopterinas/uso terapéutico , Preescolar , Dieta con Restricción de Proteínas , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Mutación , Fenilalanina/administración & dosificación , Fenilalanina/sangre , Fenilcetonurias/dietoterapia , Fenilcetonurias/genética , Fenilcetonurias/fisiopatología , Estudios Retrospectivos , EspañaRESUMEN
OBJECTIVE: To determine nitrate concentrations in drinking water in a sample of Spanish cities. MATERIAL AND METHODS: We used ion chromatography to analyze the nitrate concentrations of public drinking water in 108 Spanish municipalities with more than 50,000 inhabitants (supplying 21,290,707 potential individuals). The samples were collected between January and April 2012. The total number of samples tested was 324. RESULTS: The median nitrate concentration was 3.47 mg/L (range: 0.38-66.76; interquartile range: 4.51). The water from 94% of the municipalities contained less than 15 mg/L. The concentration was higher than 25mg/L in only 3 municipalities and was greater than 50mg/L in one. CONCLUSIONS: Nitrate levels in most public drinking water supplies in municipalities inhabited by almost half of the Spanish population are below 15 mg/L.
Asunto(s)
Nitratos/análisis , Abastecimiento de Agua , Agua/química , Ciudades , Humanos , EspañaRESUMEN
OBJECTIVES: The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children. METHODS: A prospective, multicenter, nationwide registry of new cases of CD in children <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births and as new cases per 100,000 person-years <15 years of age. RESULTS: A total of 974 new cases of CD were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total number of cases in each age group was 385, 409, and 180, respectively. Regarding clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical, and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive, respectively, for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti-gliadin antibodies. Villous atrophy was observed in 92.4% and increased intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55% had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%, DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000 live births and 54 cases per 100,000 person-years. CONCLUSIONS: In Spain, the most frequent clinical presentation of CD is the classical form, mainly diagnosed during the first 2 years of life. The observed incidence of CD in Spanish children is much higher than the present CD incidence rates observed in other European countries.