Religious dietary rules and their potential nutritional and health consequences.

BACKGROUND: The vast majority of the world population declares affiliation to a religion, predominantly Christianity and Islam. Many religions have special dietary rules, which may be more or less strictly adhered to. METHODS: Religious food rules were collected from holy books and religious websites as well as their translation into dietary practices. The literature was searched for potential associations between these rules and potential nutritional consequences. RESULTS: Jewish, Islamic and Indian religions support prolonged breastfeeding. Religious avoidance of alcohol is probably beneficial to health. When strictly applied, a few rules may lead to nutritional inadequacies, mainly in populations living in unfavourable socio-economic or environmental conditions. In Jewish and Muslim observants, animal slaughtering procedures may increase the risk of iron deficiency. Jews may be at risk of excess sodium intake related to home-prepared foods. A vegan diet, as observed by some believers, often by drifting from original precepts, or by some Hindus or Buddhists, may result in vitamin B12, calcium, iron, zinc, selenium and n-3 fatty acids deficiencies. CONCLUSION: When implemented in accordance with the rules, most religious food precepts are not detrimental to health, as suggested by the fact that they have more or less been followed for millennia. Nevertheless, some practices may lead to nutritional inadequacies, such as iron, calcium, vitamin D and vitamin B12 deficiencies. Patients with low socio-economic status, children and women of childbearing age are of particular risk of such deficiencies. Being aware of them should help health professionals to take an individualized approach to decide whether to supplement or not.

Intermediate-Term Efficacy and Tolerance of Statins in Children.

OBJECTIVES: To evaluate the intermediate-term efficacy and tolerance of statins in children and adolescents with familial hypercholesterolemia. STUDY DESIGN: A total of 131 children or adolescents treated with statins for familial hypercholesterolemia were prospectively included. The efficacy of treatment was established by the percentage of children who achieved low density lipoprotein-cholesterol (LDL-C) levels <160 mg/dL during treatment. Treatment tolerance was evaluated by the occurrence of clinical or laboratory side effects, regularity of increases in height and weight, and pubertal development. RESULTS: The median duration of treatment with statins was 4 years. A median decrease of 32% in LDL-C levels was observed (P < .0001). The therapeutic target (LDL-C <160 mg/dL) was achieved in 67% of cases. Increases in height and weight and sexual maturation were not affected by the treatment. Minor side effects were reported for 24 (18.4%) patients including 3 cases of a clinically asymptomatic increase in creatine phosphokinase (CPK) levels, 2 cases of an increase in CPK levels with muscular symptoms, 14 cases of myalgia without an increase in CPK levels, 3 cases of abdominal pain, 1 case of dysuria, and 1 case of diffuse pain. None of these side effects led to the discontinuation of statin therapy, although a change of statin was required in 7 cases. This new statin was tolerated in all cases. No patients had abnormal liver function during treatment. CONCLUSIONS: The results of this large cohort confirm the intermediate-term safety and efficacy of statin therapy in children with familial hypercholesterolemia.

Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France.

Autosomal dominant hypercholesterolemia (ADH) is a human disorder characterized phenotypically by isolated high-cholesterol levels. Mutations in the low density lipoprotein receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes are well known to be associated with the disease. To characterize the genetic background associated with ADH in France, the three ADH-associated genes were sequenced in a cohort of 120 children and 109 adult patients. Fifty-one percent of the cohort had a possible deleterious variant in LDLR, 3.1% in APOB, and 1.7% in PCSK9. We identified 18 new variants in LDLR and 2 in PCSK9. Three LDLR variants, including two newly identified, were studied by minigene reporter assay confirming the predicted effects on splicing. Additionally, as recently an in-frame deletion in the APOE gene was found to be linked to ADH, the sequencing of this latter gene was performed in patients without a deleterious variant in the three former genes. An APOE variant was identified in three patients with isolated severe hypercholesterolemia giving a frequency of 1.3% in the cohort. Therefore, even though LDLR mutations are the major cause of ADH with a large mutation spectrum, APOE variants were found to be significantly associated with the disease. Furthermore, using structural analysis and modeling, the identified APOE sequence changes were predicted to impact protein function.

Erratum to: Review of the nutritional benefits and risks related to intense sweeteners.

[This corrects the article DOI: 10.1186/s13690-015-0092-x.].

Long-term follow-up of statin treatment in a cohort of children with familial hypercholesterolemia: efficacy and tolerability.

BACKGROUND: Early identification of children with familial hypercholesterolemia (FH) makes it possible to start lipid-lowering therapy at a young age in order to prevent cardiovascular disease. Numerous randomized, often placebo-controlled, studies have assessed the efficacy and safety of statins in children with FH. OBJECTIVE: The aim of this pragmatic observational study was to evaluate pravastatin treatment efficacy and tolerability for a long period of time, and to assess how these results translate in 'real-life' clinical practice. METHODS: We analyzed all medical files of young hypercholesterolemic patients referred to two specialized French centers. This population of 185 pravastatin-treated children with FH, with a mean baseline cholesterol level above 300 mg/dL, in most of whom genetic diagnosis was achieved, was followed-up for a mean duration of 2 years 2 months. The mean age for starting pravastatin was 11 years; in one of five children, treatment was started before the age of 8 years, mostly because of severe hypercholesterolemia or a family history of coronary heart disease. RESULTS: A 16.9-19.2% decrease in total cholesterol level (21-24% for low-density lipoprotein cholesterol) was observed. Growth and puberty were not affected by statin treatment. A review of the medical files showed that 13% of children had side effects, most of which were minor; four of these children had muscular symptoms possibly related to the treatment. This frequency is lower than that observed in adults, and comparable to other studies in children. CONCLUSIONS: In this large cohort of FH children, the efficacy and tolerability of pravastatin therapy in real-life conditions was demonstrated to be similar to that in randomized controlled studies.

Intractable diarrhea with tufting enteropathy: a favorable outcome is possible.

BACKGROUND AND OBJECTIVE: Tufting enteropathy (TE) is a congenital abnormality of intestinal mucosa development characterized by severe intestinal failure requiring parenteral nutrition (PN) and, in some cases, small bowel transplantation. A few patients have had a more favorable outcome. The objective of this study was to evaluate possible correlations between histological lesion severity in duodenal biopsies and clinical outcomes in children with TE. PATIENTS AND METHODS: We retrospectively reviewed the records of patients diagnosed with TE between 1993 and 2003 at our institution based on intractable neonatal-onset diarrhea with prolonged dependence on PN and duodenal biopsy findings of villous atrophy, epithelial dysplasia with enterocyte dedifferentiation and disorganization (tufting) of the surface epithelium, and crypt abnormalities. The histological lesions were assessed semiquantitatively and compared with the clinical outcomes including dependence on PN. RESULTS: Seven children, all from consanguineous parents, were studied for a median of 6.5 years. Three were permanently weaned off PN and experienced normal growth without nutritional assistance. Initial biopsies in all 3 children showed severe diffuse histological lesions. At weaning off PN, 2 of these 3 patients had persistent, although less diffuse, histological lesions. CONCLUSIONS: Progressive weaning off PN is possible in some children with TE. In our experience, this favorable outcome was not predicted by histological lesion severity, although the lesions improved in some patients. New biomarkers for identifying the histological lesions and predicting the outcome would be useful.

[Recommendations for hypercholesterolemic children]. / Recommandations pour la prise en charge des hypercholestérolémies de l'enfant.

Some of hypercholesterolemias observed in childhood have a high risk of premature cardiovascular diseases. The monogenic dominantly inherited hypercholesterolemias such as the familial hypercholesterolemia due to mutations on LDL receptor gene corresponds to these diseases. This article, jointly elaborated by the Nouvelle Société Française d'Athérosclérose together with the Nutrition committee of the Société Française de Pédiatrie, is to propose recommendations for a screening strategy and for management of hypercholesterolemia in children. The approach of these high-risk inherited hypercholesterolemia is specified and the dietary management, the indications and supervision of lipid lowering drug therapy in children are discussed.

Natural history of Crohn's disease: comparison between childhood- and adult-onset disease.

BACKGROUND: Childhood-onset Crohn's disease (CD) might reflect a more severe form of disease. To test this hypothesis we analyzed the long-term natural history of CD in an adult cohort of patients with childhood-onset compared to adult-onset CD. METHODS: We selected 206 childhood-onset CD patients among 2992 adult patients with a diagnosis of CD established before December 31, 2000. Disease characteristics were prospectively assessed during follow-up until December 2007 and compared to adult-onset CD patients matched 2 to 1 on gender, year of CD diagnosis, and disease location. RESULTS: Compared to adult-onset CD, patients with childhood-onset CD were more likely to have a severe disease, with an increased year-by-year disease activity index (37% of patient-years in childhood-onset group versus 31% in the adult-onset group, P < 0.001). Immunosuppressant requirement was also increased with a 10-year cumulative risk of 54 +/- 3% in childhood-onset CD group versus 45 +/- 2%, in the adult-onset CD group (P < 0.001). Cumulative risks of stricturing and penetrating complications and surgical resections were not statistically different between groups. Accordingly, these events occurred at a younger age in the childhood-onset CD group. At the age of 30 years the actuarial risk of having undergone an extensive intestinal resection was 48 +/- 5% in the childhood-onset group versus 14 +/- 2% in the adult-onset group (P < 0.001). CONCLUSIONS: Patients with childhood-onset CD exhibit a more active disease and require more immunosuppressive therapy. This feature is observed irrespective of the disease location, suggesting an intrinsic more severe phenotype.

Diagnosis scoring for clinical identification of children with heterozygous familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a frequent monogenic condition characterized by progressive atherosclerosis requiring preventive therapy from childhood. In a pediatric setting, heterozygous FH (hFH) in children may not be identified from common forms of hypercholesterolemia (HC). OBJECTIVE: To elaborate a clinical scoring system for the diagnosis of hFH, defined by the presence of a disease-causing mutation of the gene for the low-density lipoprotein receptor (LDLR). PATIENTS AND METHODS: A total of 100 unrelated children (6 +/-3 years old, 43 boys, 57 girls) with type IIa HC (LDLC >130 mg/dL) and complete genetic testing (at loci for genes for LDLR, apolipoprotein B, proprotein convertase subtilisin-like kesin type 9, and apolipoprotein E) were selected for score elaboration. Of 60 criteria from clinical records and family questionnaires, predictors of having hFH were estimated by logistic regression analysis. Scores were validated in 38 other unrelated children with HC. RESULTS: Three independent predictors of hFH were identified according to the LDLR genotype (50 Microt+/50 Microt-): low-density lipoprotein cholesterol before (262 vs 178 mg/dL, P < 0.001) and after (225 vs 142 mg/dL, P < 0.001) 3 months or more of a lipid-lowering diet, combined with parental statin usage (odds ratio 6.2; 95% confidence interval 1.4-28.3; P = 0.018). High precision and accuracy of the scoring system (area under the receiver operating characteristic curve = 0.94; 95% confidence interval 0.91-0.98) were translated into 4 probability classes (definite/probable/possible/improbable hFH) with a false-negative rate of 12%. CONCLUSIONS: A score distinguishing hFH from common HC provides a simple tool for appropriate clinical decision and care in high-risk children.

Plasma citrulline concentration reflects enterocyte mass in children with short bowel syndrome.

Plasma citrulline was recently shown to reflect the residual functional enterocyte mass in various situations characterized by intestinal failure. However, few data are available in children with short bowel syndrome. The objective of this study was to assess the value of citrulline assays in this situation. Prospective plasma citrulline assays were performed in 31 children with short bowel syndrome. Median age was 16 mo (range, 1 mo to 15 y), and median follow-up was 14 mo (6-40 mo). The energy supplied by parenteral nutrition (PN), served to assess intestinal failure severity. Plasma citrulline at inclusion showed a positive correlation with residual short bowel length. Subsequent values correlated negatively with intestinal failure severity. Plasma citrulline increased over time during or after weaning from PN (from 15.8 +/- 11.5 microM to 19.3 +/- 3.8 microM) but remained stable and low in patients who continued to need PN (6.5 +/- 3.0 microM at inclusion and 7.7 +/- 6.0 microM at last follow-up). No weaned patients had a residual short bowel length less than 40 cm and plasma citrulline less than 11 microM. Our findings constitute the first evidence that serial plasma citrulline assays help to monitor residual small bowel adaptation in children.

Association of arterial stiffness and endothelial dysfunction with metabolic syndrome in obese children.

OBJECTIVE: We investigated whether metabolic syndrome, defined in 3 different ways (2 commonly used and 1 novel) is associated with arterial alterations in obese children. STUDY DESIGN: The study group comprised 384 obese children age 2.5 to 18 years. Blood pressure, fasting blood glucose, blood insulin, plasma lipids, and body composition were measured. Noninvasive ultrasound measurements were obtained in 161 patients to investigate arterial mechanical properties and endothelial function. RESULTS: The prevalence of metabolic syndrome was 10.4%. Intima-media thickness correlated positively with low-density lipoprotein cholesterol (r = .21; P < .01) and negatively with high-density lipoprotein cholesterol (r = -.17; P < .05). In adolescents (11 to 18 years), cross-sectional vascular compliance correlated negatively with abdominal fat (r = -.22; P = .02). The only synergistic effects among individual metabolic syndrome components was an effect of insulinemia and systolic blood pressure on cross-sectional compliance (4.05; P < .05). No significant difference in vascular variables was found between the patients with and without metabolic syndrome using any of the 3 definitions. CONCLUSION: Metabolic syndrome in obese children is not related to arterial variables, whereas several of its individual components are associated with vascular alterations. These data suggest that the value of the metabolic syndrome as a predictor of future cardiovascular events in children remains to be prospectively evaluated. In the meantime, individual cardiovascular risk factors should be evaluated and controlled.

Pulmonary function and sleep-related breathing disorders in severely obese children.

BACKGROUND & AIMS: To evaluate the frequency of pulmonary function and sleep-breathing disorders in severely obese children and to search for their association with obesity phenotypes. METHODS: Sleep studies and spirometry were performed for 54 severely obese children. RESULTS: Upper airway resistances (RAWs) were increased with RAW>200% and forced 25s expiratory volume<80% in 83% and 60% of individuals, respectively. A decrease in functional residual capacity (FRC)<80% was found in 43%. Fifty-two percent of the children had a desaturation index>10 during sleep, and 41% of children presented at least one of three severity criteria (snoring index>300 per hour, respiratory events index (REI)>10 and arousal index>10). Univariate analyses showed a positive correlation between snoring index and BMI Z-score and neck/height ratio (P=0.01 and 0.04, respectively) as between REI and the same parameters (P=0.01 and 0.03, respectively). In a multivariate model with BMI Z-score, NHR still correlated with the snoring index (P=0.02) and REI (P=0.01). CONCLUSIONS: In our cohort, obese children showed frequent pulmonary function and sleep-breathing disorders. The later were associated with impaired upper airway respiratory conductance.

Insulin resistance and ferritin as major determinants of abnormal serum aminotransferase in severely obese children.

OBJECTIVES: Liver involvement is a common complication of obesity related in part to insulin resistance. The role of ferritin has not been investigated in children. The aim was to determine the prevalence of liver enzyme abnormalities in severely obese children and to look for relationships between fat mass distribution, insulin resistance, and plasma ferritin. METHODS: 197 children with severe obesity (defined as a body mass index Z-score (BMI-Z) > 3.0) were studied prospectively from 2001 to 2004. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were measured, as well as anthropometric characteristics: blood pressure; body composition by dual energy X-ray absorptiometry, and plasma fasting glucose, insulin, leptin, lipid, and ferritin concentrations. RESULTS: Serum ALT and AST values were abnormal in 23 (11.7%) and 13 (6.6%) children, respectively. By univariate analysis, serum ALT and AST values were positively correlated with android fat mass distribution (P < 0.0001 and P = 0.005, respectively) after adjustment for age, sex, ethnicity, and Tanner stage. Using the same model, a positive correlation and a positive trend linked plasma ferritin to serum AST (P = 0.02) and serum ALT (P = 0.06), respectively. Serum ALTwas positively correlated to insulin resistance (P = 0.03). Using a multivariate model, with the android/gynoid fat mass ratio as an additional independent variable, ferritin remained correlated with serum AST and ALT (P = 0.001 and P = 0.008, respectively). CONCLUSIONS: Abnormal serum aminotransferase values are uncommon in severely obese children in France. Android fat mass distribution, insulin resistance, and higher ferritin concentrations are significantly associated with liver abnormalities in our cohort.

Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia.

Autosomal dominant hypercholesterolemia (ADH) is a frequent (1/500) monogenic inherited disorder characterized by isolated elevation of LDL leading to premature cardiovascular disease. ADH is known to result from mutations at two main loci: LDLR (encoding the low density lipoprotein receptor), and APOB (encoding apolipoprotein B100), its natural ligand. We previously demonstrated that ADH is also caused by mutations of the PCSK9 (proprotein convertase subtilisin/kexin type 9) gene that encodes Narc-1 (neural apoptosis-regulated convertase 1). However, the role of this novel disease locus as a cause of hypercholesterolemia remains unclear. In the present study, we analysed the PCSK9 coding region and intronic junctions in 130 adult or pediatric patients with ADH, previously found as being non LDLR/non APOB mutation carriers. Four novel heterozygous missense variations were found: c.654A>T (p.R218S), c.1070G>A (p.R357H), c.1405C>T (p.R469W), and c.1327G>A (p.A443T). All mutations were absent in 340 normolipidemic controls. Except for the A443T, all mutations are nonconservative and modify a highly conserved residue. Segregation with hypercholesterolemia is incomplete in one pedigree. Type and severity of hyperlipidemia and of cardiovascular disease could vary among subjects from the same family. Finally, the proband carrying the R357H mutation exhibited very high plasma cholesterol during pregnancy, whereas the proband carrying the p.R469W mutation exhibited a severe phenotype of hypercholesterolemia in combination with a LDLR mutation resulting from a frameshift at residue F382 (1209delC). These observations suggest that variations in PCSK9 are a rare cause of non LDLR/non APOB ADH (approximately 2.3%) and that additional environmental or genetic factors may contribute to the phenotype caused by PCSK9 missense mutations in humans.

[Allergy to food colouring. A prospective study in ten children]. / Allergie aux colorants alimentaires chez l'enfant. Etude prospective chez dix enfants.

In order to know more about allergy to food colouring, we conducted a prospective open study over 8 months in a group of 10 atopic children with repeated urticaria. The mean age was 6.5 years (4.2 - 13.5 years). The diagnosis was based on oral challenge tests along with hisory taking there were 3 cases of allergy to food colourings. Clinical features were mainly skin symptoms, sometimes associated with GI manifestations which were not only rare (1 case in our series) but also non specific. Colourings-free diet was recommended in consequence. It resulted in the disappearance of the symptoms in a child (Red cochineal) and their regression in the two others (Red cochineal, Red beet) with a follow up of 8 months and 3 months respectively.

Role of the DGAT gene C79T single-nucleotide polymorphism in French obese subjects.

Acyl-coenzyme A, diacylglycerol acyltransferase (DGAT), is a key enzyme involved in adipose-cell triglyceride storage. A 79-bp T-to-C single-nucleotide polymorphism (SNP) on the 3' region of the DGAT transcriptional site has been reported to increase promoter activity and is associated with higher BMI in Turkish women. To validate the possible role of this genetic variant in obesity, as well as the variant's possible cellular-functional significance, we performed an association study between the T79C change and several obesity-related phenotypes in 1357 obese French adults and children. The prevalence of the T79C SNP was similar between obese adults and children when each group was compared with the controls. (CC genotype carrier frequencies were 0.25 to 0.29 in the obese groups and 0.21 in controls; p > 0.05.) In each of the obese adult and child groups studied, the T79C variant was not found to be associated with any of the obesity-related phenotypes tested. Although the T79C SNP of the DGAT gene was studied in several groups of white subjects, the association between this SNP and obesity-related phenotypes, previously described, was not confirmed in our population.

[Anticholesteremic agents in children]. / Les médicaments hypocholestérolémiants chez l'enfant.

The treatment of hypercholesterolaemia in children is often discussed as part of the primary prevention strategy for premature coronary disease in adults. Cholesterol-lowering drugs are appropriate in children with hereditary autosomal dominant diseases such as familial hypercholesterolaemia, familial Apo B100 deficiency, or combined familial dyslipidaemia. Indeed, these diseases are associated with a high risk of cardiovascular attacks in young adults. In children suffering from these diseases, cholesterol-lowering drugs are considered when the plasma low density-lipoprotein (LDL)-cholesterol concentration remains above 190 mg/dL after a 6-month dietary treatment. The drug of first choice remains bile acid-binding resines (colestyramine) because their efficacy and safety are well documented in children. HMG-CoA reductase inhibitors can be used in children older than 8 or 9 years of age in cases of an altered observance of colestyramine treatment, but their long-term tolerance is unknown. Fibrates are also efficient, however, their safety has not been evaluated in controlled studies through in children.

Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.

Familial hypercholesterolemia (FH), a frequent monogenic condition complicated by premature cardiovascular disease, is characterized by high allelic heterogeneity at the low-density lipoprotein receptor ( LDLR) locus. Despite more than a decade of genetic testing, knowledge about intronic disease-causing mutations has remained limited because of lack of available genomic sequences. Based on the finding from bioinformatic analysis that Alu repeats represent 85% of LDLR intronic sequences outside exon-intron junctions, we designed a strategy to improve the exploration of genomic regions in the vicinity of exons in 110 FH subjects from an admixed population. In the first group of 42 patients of negative mutation carriers, as previously established by former screening strategies (denaturing gradient gel electrophoresis, DNA sequencing with former primers overlapping splice-sites, Southern Blotting), about half ( n=22) were found to be carriers of at least one heterozygous mutation. Among a second group of 68 newly recruited patients, 27% of mutation carriers ( n=37) had a splicing regulatory mutation. Overall, out of the 54 mutations identified, 13 were intronic, and 18 were novel, out of which nearly half were intronic. Two novel intronic mutations (IVS8-10G-->A within the polypyrimidine tract and IVS7+10G-->A downstream of donor site) might create potential aberrant splice sites according to neural-network computed estimation, contrary to 31 common single nucleotide variations also identified at exon-intron junctions. This new strategy of detecting the most likely disease-causing LDLR mutations outside of Alu-rich genomic regions reveals that intronic mutations may have a greater impact than previously reported on the molecular basis of FH.