Estatus vitamínico actual en pacientes pediátricos y adultos jóvenes con fibrosis quística / Current vitamin status in pediatric and young adult patients with cystic fibrosis

Introducción y objetivos: Las enfermedades como la fibrosis quística (FQ) que asocian malabsorción de grasas, precisan de suplementación de vitaminas liposolubles para evitar su deficiencia. El objetivo de nuestro objetivo fue conocer el estado de las vitaminas A, D y E en pacientes pediátricos y adultos con FQ. Pacientes y métodos. Estudio multicéntrico descriptivo y transversal, realizado en cinco hospitales nacionales, 126 pacientes con FQ sin agudización respiratoria, con edades entre 5 y 38 años. Los niveles de retinol y a-tocoferol se compararon con la población de referencia NHANES para establecer 3 categorías: deficientes (< P5), normales (P5-P95) y elevados (>P95); se consideró deficiencia de vitamina D si los niveles de 25 OH vitamina D fueron menores de 30 ng/ml. Resultados: La mediana de edad fue 14,2 años. El 51% eran varones y un 13% suficientes pancreáticos. El 56% presentaba deficiencia de al menos una vitamina liposoluble. La más frecuente fue la vitamina D (48%), seguida de la E (16%) y por último la vitamina A (11%). Los suficientes pancreáticos tenían niveles de vitamina D más elevados que los insuficientes. La proporción de pacientes con algún grado de deficiencia fue mayor en los pacientes adultos y sus niveles de vitamina D fueron más bajos. Conclusiones: A pesar de recibir una suplementacion adecuada, más de la mitad de los pacientes no alcanzaron niveles óptimos de vitaminas liposolubles. La función pancreática y la edad son dos factores a tener en cuenta a la hora de analizar el estatus vitamínico de estos pacientes

Introduction and objectives: Pancreatic insufficiency and fat and bile malabsoption render individuals with Cystic Fibrosis (CF) at risk for fat-soluble vitamin malabsoption. Our objective was to determine the status of vitamins A, D and E in pediatric and adult patients with CF. Patients and methods. Descriptive cross-sectional study. 126 patients without pulmonary exacerbation, aged between 5 and 38, were recruited in five national Cystic Fibrosis units. Retinol and a-tocopherol levels were compared with NHANES reference values to establish 3 categories: deficient (< P5), Normal (P5- P95) and elevated (> P95), vitamin D was considered deficient if 25 OH vitamin D < 30 ng/ml. Results: The median age was 14.2 years. 51% were male and 13% pancreatic sufficient. 56% had at least one vitamin deficiency. The most frequent was vitamin D (48%), followed by E (16%) and finally vitamin A (11%). Pancreatic sufficient had higher vitamin D levels than insufficient. The proportion of patients with any degree of vitamin deficiency was greater in adults and their vitamin D levels were lower. Conclusions: Despite adequate supplementation, more than half of patients did not reach optimal vitamins levels. Pancreatic status and age were two factors to take into account when analyzing vitamin status of these patients

Síndrome de Gilbert: estudio de 12 observaciones y revisión de la bibliografía médica / Gilbert’s syndrome: a study of 12 observations and review of the literature

El síndrome de Gilbert es el hallazgo de hiperbilirrubinemia indirecta leve-moderada con pruebas de función hepática normales y sin signos de hemólisis. Es un trastorno hereditario del metabolismo de la bilirrubina, benigno, con una prevalencia mundial cercana al 10%. Tiene un patrón de herencia variable, con polimorfismo genético. Se diagnostica mediante pruebas confirmatorias de provocación, como la prueba del ayuno, aunque el diagnóstico definitivo es genético. Su pronóstico es bueno y actualmente se discute sobre los diversos efectos de la hiperbilirrubinemia. En este artículo, se revisan los casos diagnosticados de síndrome de Gilbert en el servicio de pediatría de un hospital universitario en los últimos años, y se describen las principales características halladas

Gilbert’s syndrome is characterized by a mild or moderate elevation of unconjugated bilirubin, with normal liver function and no evidence of hemolysis. It is a benign inherited disorder of bilirubin metabolism, with a worldwide prevalence of nearly 10%. It has a variable pattern of inheritance, with genetic polymorphism. Diagnosis is based on a confirmatory provocation test, such as the fasting test, although the definitive diagnosis requires a genetic study. The prognosis is good and, at the present time, the varied effects of hyperbilirubinemia are a matter of debate. The cases of Gilbert’s syndrome diagnosed in the pediatric service of a university hospital in recent years were reviewed and the main characteristics are described

HLA system. Phenotypic and gene frequencies in celiac and healthy subjects from the same geographical area.

OBJECTIVE: To compare the phenotypic and gene frequencies of the HLA system in celiac and healthy subjects the same geographical area. PATIENTS AND METHODS: HLA A, B, C, DR and DQ phenotypic and gene frequencies have been estimated in 38 celiac children and healthy subjects. The HLA typing has been done according to the microlymphocytotoxicity assay. The individual HLA antigen frequencies in each group have been compared by Chi-square test using Yates correction. For each specificity, the strength of association with celiac disease has been estimated by Odds Ratio and 95% confidence limit. RESULTS: The comparative study of both population show increased phenotypic and gene frequencies among celiac patients and significant differences compared with healthy subjects for B8, Cw7, DR3, DR7 and DQ2. On the contrary, Cw4 and DQ1 phenotypic and gene frequencies are significantly increased in the control population. CONCLUSIONS: Our findings support the role of HLA antigens as predisposing factors for celiac disease. The presence of Cw4 and DQ1 can be a protective factor against such disease.

[Two loci HLA haplotypes in celiac children. Linkage imbalance and haplotype frequencies. Comparative study with a control population]. / Haplotipos HLA de dos loci en niños celíacos. Desequilibrio de linkage y frecuencias haplotípicas. Estudio comparativo con una población control.

OBJECTIVE: Celiac disease is closely correlated with certain human lymphocyte antigen (HLA) alleles. The aim of this study was to compare linkage disequilibrium parameters and the frequencies of the two loci haplotypes: HLA A/B, A/C, A/DR, A/DQ; HLA B/C, B/DR, B/DQ; HLA C/DR, C/DQ and HLA DR/DQ in children with celiac disease and in a control population within the same geographical area. METHODS: Thirty-eight children with celiac disease, aged 5months to 18years at diagnosis, were HLA typed by microlymphocytotoxicity assay using T and Bcells separated by monoclonal antibody labeled immunomagnetic particles. The frequency of each haplotype of two loci (Hij) depends on the frequency of each allele (pi and pj) and on a correction factor delta, according to the formula: Hij5 Dij1(pi3pj). The existence of a correction factor delta, or linkage disequilibrium, was assessed by a chi square test using 2 X 2contingency tables for gametic association. RESULTS: Among children with celiac disease the most frequent and significant haplotypes were A1/B8, A9/B5, A19/B12, A28/B22, A28/Cw1, A9/DQ3, B8/Cw7, B18/Cw5, B22/Cw1, B5/DR5, B8/DR3, B12/DR7, B5/DQ3, DR3/DQ2, DR4/DQ8 (3) and DR5/DQ3, showing a positive linkage disequilibrium. Negative linkage disequilibrium was found between B18/Cw7, B12/DR3, Cw4/DR3 and DR3/DQ3. CONCLUSIONS: Our findings show that the frequency of A1/B8,A19/B12, B8/DR3,B12/DR7 and DR3/DQ2 haplotypes is higher in children with celiac disease than in the control population and suggest that these two loci haplotypes confer susceptibility to celiac disease.

Sistema hla. Frecuencias fenotípicas y génicas en celíacos y controles de la misma área geográfica / Hla system. Phenotypic and gene frequencies in celiac and healthy subjects from the same geographical area

Objetivo: comparar las frecuencias fenotípicas y génicas del sistema HLA en celíacos y controles normales de la misma área geográfica. Pacientes y métodos: se han determinado y comparado las frecuencias fenotípicas y génicas de los loci HLA-A, B, C, DR y DQ de 38 niños celíacos y de la población control, de la misma zona geográfica. Para su valoración se ha utilizado la técnica de microlinfocitotoxicidad. Las frecuencias antigénicas de cada grupo han sido comparadas mediante el test de Chi cuadradro y corrección de Yates. Para cada especificidad la fuerza de asociación ha sido estimada por la odds ratio y límite de confianza del 95 por ciento. Resultados: el estudio comparativo entre ambas poblaciones muestra frecuencias fenotípicas y génicas más elevadas en los celíacos y diferencias significativas con respecto a la población control para B8, Cw7, DR3, DR7 y DQ2. Por el contrario, las frecuencias fenotípicas y génicas de Cw4 y DQ1 son significativamente mayores en la población control. Conclusiones: estos hallazgos apoyan el papel de los antígenos HLA en la susceptibilidad a la enfermedad celíaca. La presencia de Cw4 y DQ1 puede ser un factor de protección frente a la misma (AU)

Haplotipos HLA de dos loci en niños celíacos. Desequilibrio de linkage y frecuencias haplotípicas. Estudio comparativo con una población control / Two loci HLA haplotypes in celiac children and healthy subjects. Estimate of linkage disequilibrium parameters and haplotype frequencies

OBJETIVO: La enfermedad celíaca está estrechamente relacionada con ciertos antígenos HLA. El objetivo de este estudio es valorar el desequilibrio de linkage existente entre los diferentes antígenos y las frecuencias de los haplotipos de dos loci: HLA A/B, A/C, A/DR, A/DQ; HLA B/C, B/DR, B/DQ; HLA C/DR, C/DQ y HLA DR/DQ, en niños con enfermedad celíaca y en población control de la misma zona geográfica. PACIENTES Y MÉTODOS: Se han determinado y comparado el valor del desequilibrio de linkage y frecuencias de los haplotipos de dos loci en 38 niños celíacos, de edades comprendidas al diagnóstico entre 5 meses y 18 años y en la población control de la misma región geográfica (Aragón, región del noreste de España). Para su estudio se ha utilizado la técnica de microlinfocitotoxicidad. La frecuencia de cada haplotipo de dos loci (Hij) depende de la frecuencia génica de cada alelo (pi y pj) y de un factor de corrección D, según la fórmula: Hij5 Dij1 (pi3 pj). La estimación de la asociación entre gametos se ha determinado mediante tablas de contingencia 2 3 2, realizadas independientemente para cada una de las combinaciones fenotípicas entre especificidades de dos loci diferentes. RESULTADOS: En los enfermos celíacos, los haplotipos más frecuentes y significativos son: A1/B8, A9/B5, A19/B12, A28/B22, A28/Cw1, A9/DQ3, B8/Cw7, B18/Cw5, B22/Cw1, B5/DR5, B8/DR3, B12/DR7, B5/DQ3, DR3/DQ2, DR4/DQ8 (3) y DR5/DQ3. Entre los haplotipos A/DR no se ha encontrado ninguno significativo. Los haplotipos B18/Cw7, B12/DR3, Cw4/DR3 y DR3/DQ3 tienen un desequilibrio de linkage negativo estadísticamente significativo. CONCLUSIÓN: Del estudio comparativo entre niños celíacos y población se concluye que las asociaciones de los haplotipos A1/B8,A19/B12, B8/DR3, B12/DR7 y DR3/DQ2 son significativamente más frecuentes en los celíacos que en la población control y su presencia puede predisponer al padecimiento de dicha enfermedad (AU)

[Effect of apolipoprotein E phenotypes on the response to dietary treatment of children with hypercholesterolemia]. / Efecto de los fenotipos de la apolipoproteína E en la respuesta al tratamiento dietético en niños con hipercolesterolemia.

OBJECTIVE: Our objective was to determine if apo E phenotypes have any effect on the serum lipoprotein response to dietary intervention in children with hypercholesterolemia. PATIENTS AND METHODS: We have selected 76 children with total serum cholesterol levels higher than 200 mg/dL. At diagnosis, each patient met with a member of our clinic that established dietary recommendations (total and saturated fat intake: 30 and 10%, respectively, of total energy intake). At diagnosis and after 6 months of therapy we determined a lipoprotein profile. RESULTS: After 6 months of therapy, there was only a significant change in children with phenotype E3/E4, with significant decreases in serum total cholesterol (from 247 +/- 43 to 231 +/- 47 mg/dL, p = 0.002), LDL-cholesterol (from 164 +/- 47 to 149 +/- 48 mg/dL, p = 0.002) and triglycerides (from 81 +/- 36 to 71 +/- 31 mg/dL, p = 0.028) concentrations. Absolute and % delta differences in serum lipoprotein concentrations before and after dietary treatment do not show significant differences between apo E phenotype groups. CONCLUSIONS: In the group studied, apo E phenotypes do not determine the response to a low-fat, low-cholesterol diet in children with hypercholesterolemia. To know the factors that determine the variability in the response to dietary intervention in children with hypercholesterolemia it would be interesting to study other familial and genetic factors.

[Lipoprotein profile determinants in children and adolescents from a lipid consultation clinic. The impact of diet, body composition and physical activity]. / Determinantes del perfil lipídico en niños y adolescentes asistidos en una consulta de lípidos. Importancia de la dieta, composición corporal y actividad física.

OBJECTIVE: Diet, physical activity, physical fitness and body composition are factors that contribute to lipid disorders; however, we do not know whether they are relevant in children of the general population and in children with dyslipoproteinemias. PATIENTS AND METHODS: We have studied all of these factors in 89 children, aged 4.0 to 20.0 years. Children were divided into two groups: 1) Normocholesterolemics (total cholesterol < 225 mg/dL) and 2) Hypercholesterolemics (total cholesterol > or = 225 mg/dL). RESULTS: In normocholesterolemic children, the main determinants of total and low-density lipoprotein cholesterol were height and cholesterol intake, which explained both 50 and 32% of its variability, respectively. The main determinants of high density lipoprotein cholesterol were blood pressure after submaximal loading and fat mass, which explained 50% of the variability. In hypercholesterolemic children, fat and carbohydrate intake and physical activity explained more than 90% of the variability of total and low density lipoprotein cholesterol. Resting energy expenditure explained 40% of the variability of high density lipoprotein cholesterol. CONCLUSIONS: In the treatment of children and adolescents with dyslipoproteinemias, we must emphasize not only dietary intake, but also physical activity. To increase high density lipoprotein cholesterol we must also improve physical fitness and decrease the amount of body fat mass.

[Atherogenic risk factors in children of parents with ischemic heart disease]. / Factores de riesgo aterogénico en hijos de padres con cardiopatía isquémica.

We have studied serum lipid levels and dietetic intake in 38 children whose parents had ischemic heart disease (HPCI) before 55 years of age and in a control group (n = 114). In the HPCI group, 25% had serum levels of total cholesterol higher than 200 mg/dl; only 2 children presented elevated levels of LDL and apo B. Dietetic intakes in both groups were similar, with a high protein (16-17% of calories) and fat (39-42% of calories) intake and a low carbohydrate intake (40.46% of calories). In both groups the percentage of monounsaturated fat was higher than other types of fat. The most frequent phenotype in the HPCI group was IIa (8 children). Only 1 child showed a IIb phenotype. This finding may be due to the variability of this phenotype in the same individual throughout life. In the families (n = 8), we have detected 2 families with polygenic hypercholesterolemia (HP), 2 others with familial combined hyperlipidemia (HFC) and 4 without family history of hyperlipidemia. Taking into account the lipid profile in children of the HPCI group, we have detected the presence of familial dysliproproteinemias. It appears that dietetic intake is not an atherogenic risk factor in these patients.

[Primary dyslipoproteinemias in a child-adolescent population of Aragón detected by two methods: selective search and targeted search]. / Dislipoproteinemias primarias en una población infanto-juvenil aragonesa detectadas mediante dos estrategias: búsqueda selectiva y búsqueda oportunista.

A series of 439 children (245 boys and 194 girls) ranged between 2.0 and 18.0 years of age have been studied January 1987 to April 1990. They belonged to four groups: I) 306 children (163 boys and 143 girls), "control group"; II) 31 children (22 boys and 9 girls) whose parents had some type of dyslipoproteinemia (HPDLP); III) 38 children (24 boys and 14 girls) whose fathers were survivors of myocardial infarction occurred before 55 years of age (HPCI); and IV) 43 children (23 boys and 20 girls) who had, at least in two occasions, more than three months of time separated between then, over 200 mg/dL of total serum cholesterol levels detected by opportunist search (HDC). For children's identification of risk factors to develop atherosclerotic disease during adult life, two different types of strategy has been utilised. One, "selective search", taking into account children of groups II (HPDLP) and III (HPCI). Other, "opportunist search", taking into consideration children of group IV (HDC). The most frequent primary dyslipoproteinemia between the families of children with high serum levels has been Polygenic Hypercholesterolemia (HP). In the second place were both Familial Hypercholesterolemia (HF) an Familial Combined Hyperlipidemia (HFC). A family with Mixed Hyperlipidemia (HM) was also identified. Familial aggregation, with relation to serum lipid levels, were detected in children of the three groups: HPDLP, HPCI and HDC, as it is reported by another authors. Our results suggest the genetic alterations may contribute to the presence of different types of dyslipoproteinemia in children.

[Hyperapo-beta-emia in children. Study of 17 families]. / Hiperapo-beta-emia en niños. Consideraciones a propósito de 17 familias.

Apolipoprotein (apo)-beta is an atherosclerotic risk factor in adults and children. In families with Familial Combined Hyperlipidemia (FCH) it has been described as a lipoprotein phenotype called Hyperapobetalipoproteinemia (Hyperapo-beta) and characterized by increased numbers of small, dense and apo-beta enriched low density lipoproteins. In our Lipids Clinic, we have studied 267 children, but for the purpose of this paper we have only taken into account the 19 of these children who showed increased plasma total apo-beta levels (Hyperapo-beta-emina). To investigate the type of dyslipoproteinemia of these children, we divided them into two groups: 1) Group 1: 10 children with apo-beta levels greater than mean + 2 standard deviations (SD); 2) Group 2: 9 children with apo-beta levels greater than mean + 3 SD. We have also studied the fathers, mothers, brothers and sisters of all the children. Only one child (Group 1) had type IIb hyperlipoproteinemia. The other children had type IIa hyperlipoproteinemia. In each group, 4 families had FCH and the others had either Familial Hypercholesterolemia or Polygenic Hypercholesterolemia. Families with FCH could also have hyperapo-beta. It is possible that in the future some children of FCH families and those with type IIa hyperlipoproteinemia will have increased plasma triglyceride levels. This could be prevented by a proper diet.

[The value of diagnostic endoscopy in the treatment of intestinal polyps in the child]. / Valor de la endoscopia en el diagnóstico y tratamiento de los pólipos del tracto intestinal en el niño.

The polyps of the digestive tract, with the exception of the juvenile ones, are not often found in children. Out of 762 endoscopies paediatric patients carried out, 31 were seen to be affected by digestive polyps, of which 16 were juvenile. The rest belonged to other types, among which 5 adenomas are included. In this paper, clinical aspects are analysed, pointing out also the value of the endoscopy as choice method not only for diagnosis but also for treatment of polyps.

[Plasma fatty acids in children with cystic fibrosis]. / Acidos grasos plasmáticos en niños con fibrosis quística.

A study of plasmatic fatty acids was carried out on a group of paediatric patients suffering from cystic fibrosis. These data have been compared with those obtained by others authors. High levels of saturated fatty acids and a reduction of polyunsaturates have been found. The ratio of eicosatrienoic acid to arachidonic acid is high in this group of patients, which indicates a certain lack of essential fatty acids.

[Pulmonary gammagraphy in children with cystic fibrosis]. / Gammagrafía pulmonar en niños afectos de fibrosis quística.

An analysis is carried out of the findings from the radioisotopic lung scans of 16 children suffering from cystic fibrosis (CF), 10 boys and 6 girls, with an age range of between 3.5 and 14.2 years and an evolution time of between 1.2 and 9.9 years. The radioisotopic lung scan study shows lung perfusion defects in 14 of the 16 children (87%), the pulmonary vertices being more greatly affected, especially in the left lung (81%). We revised current aspects of radioisotopic lung scanning in paediatrics and evaluated the great importance of this test as a means of detecting CF and its evolution.

[Evaluation of the inflammatory and nutritional status in children with cystic fibrosis]. / Evaluación del estado nutricional-inflamatorio en niños afectos de fibrosis quística.

The authors present a system for the appraisal of the nutritional and inflammatory condition in patients suffering from cystic fibrosis (CF) in the phase of apparent inactivity of pulmonary infection, using a system of indices based on the quantification of some plasmatic proteins. The plasmatic appraisals of 4 visceral proteins (albumin, thyroxine-binding prealbumin, retinol-binding protein and transferrin) and, as well, of 5 proteins of the acute phase (alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-2-macroglobulin, haptoglobin and ceruloplasmin) were obtained in a control group of 16 healthy children and in another of 14 children affected by CF. With the proteic plasmatic appraisals of the control group, the knowledge of their biological value and after a statistical-mathematical analysis, the most sensitive, specific and independent proteins were determined for evaluating the nutritional and inflammatory condition, obtaining two simple formulas which were denominated Nutritional-Inflammatory Prognostic Indices (NIPI) A and B (NIPI A = alpha-1-acid glycoprotein + haptoglobin/albumin + prealbumin; NIPI B = haptoglobin/albumin). From the analysis of the results, it can be deduced that the children with CF are affected by an inflammatory process, very probably infectious.