Nonalcoholic Fatty Liver Disease in Children with Excess of Weight

International audienceRationale:Obesity in children is a public health problem. Obesity can be complicated by liver damage. The aim of our study was to investigate the nonalcoholic fatty liver disease (NAFLD) in children with excess of weight and factors associated with NAFLD.Methods:Children with overweight and obesity had measures of body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting serum glucose and lipids (total cholesterol, HDL-c, LDL-c and triglycerides) and hepatic function (ASAT, ALAT, γ GT). The NAFLD was researched with ultrasound and predictive score of NAFLD was calculated : hepatic steatosis index (HSI). Metabolic syndrome was diagnosed with WC, BP, serum glucose, HDL-c and triglycerides. Statistical analysis used Student ’ s t tests, Chi2 and logistic regression.Results:Seventy-six children were included, 46% of males with a mean age of 11.3 ± 3.4 years. The mean BMI was of 29.1 ± 5.9 kg/m2 and 77.6% of children were obese. The serum glucose and lipid levels were no different between overweight and obese children. In contrast, the ALAT/ASATratiowas higher in obese (1.0 ± 0.4 vs. 0.8 ± 0.3, p = 0.02). The HSI score was higher in obese (40.0 ± 7.0 vs. 30.2 ± 6.8, p < 0.0001). With ultrasound NAFLD was found in 38.2%, 43.4% in obesity. Metabolic syndrome was found in 50.0% in children with NAFLD.The HSI was positive in 92.0% in children with NAFLD. WC (OR = 1.09 [95% CI: 1.09 – 1.16]; p = 0.0034), systolic BP(OR = 1.06 [95% CI: 1.01–1.12]; p = 0.03) and triglycerides (OR = 1.03 [95% CI 1.001–1.05]; p = 0.016) were positively associated with NAFLD.Conclusion:Over one third of children had a NAFLD. NAFLD was two time more present in obesity. Criteria of metabolic syndrome (WC, systolic BP and triglyceride) were positively associated with NAFLD. Considering the risk of progression, it seems essential to follow these children mainly in case of obesity with metabolic syndrome and continue this follow up in adulthoo

Management and screening of childhood obesity : practices and expectations of general practitioners and liberal pediatricians.

International audienc

Vision de l'obésité pédiatrique par les médecins généralistes.

International audienc

Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid

Thyroid dysgenesis is the most common cause of congenital hypothyroidism, a relatively frequent disease affecting 1 in 3000-4000 newborns. Whereas most cases are sporadic, mutations in transcription factors implicated in thyroid development have been shown to cause a minority of cases transmitted as monogenic Mendelian diseases. PAX8 is one of these transcription factors, and so far, five mutations have been identified in its paired domain in patients with thyroid dysgenesis. We have identified a novel mutation of PAX8, in the heterozygous state, in a father and his two children both presenting with congenital hypothyroidism associated with an in-place thyroid of normal size at birth. In addition, one of the affected siblings displayed unilateral kidney agenesis. The mutation substitutes a highly conserved serine in position 54 of the DNA-binding domain of the protein (S54G mutation) by a glycine. Functional analyses of the mutant protein (PAX8-S54G) demonstrated that it is unable to bind a specific cis-element of the thyroperoxidase gene promoter in EMSAs and that it has almost completely lost the ability to act in synergy with Titf1 to transactivate transcription from the thyroglobulin promoter/enhancer. These results indicate that loss of function mutations of the PAX8 gene may cause congenital hypothyroidism in the absence of thyroid hypoplasia.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations.

International audienceCONTEXT: Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare metabolic disorder characterized by hyperphosphatemia and localized hyperostosis. HHS is caused by mutations in GALNT3, which encodes UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- acetylgalactosaminyltransferase 3. Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes. OBJECTIVE: Our objective was to identify mutations in FGF23 or GALNT3 and determine serum FGF23 levels in an HHS patient. DESIGN: Mutation detection in FGF23 and GALNT3 was performed by DNA sequencing, and serum FGF23 concentrations were measured by ELISA. PATIENTS OR OTHER PARTICIPANTS: A 5-year-old French boy with HHS and his family members participated. RESULTS: The patient presented with painful cortical lesions in his leg. Radiographs of the affected bone showed diaphyseal hyperostosis. The lesional tissue comprised trabeculae of immature, woven bone surrounded by fibrous tissue. Biochemistry revealed elevated phosphate, tubular maximum rate for phosphate reabsorption per deciliter of glomerular filtrate, and 1,25-dihydroxyvitamin D levels. The patient was a compound heterozygote for two novel GALNT3 mutations. His parents and brother were heterozygous for one of the mutations and had no biochemical abnormalities. Intact FGF23 level in the patient was low normal, whereas C-terminal FGF23 was elevated, a pattern similar to TC. CONCLUSION: The presence of GALNT3 mutations and elevated C-terminal, but low intact serum FGF23, levels in HHS resemble those seen in TC, suggesting that HHS and TC are different manifestations of the same disorder. The absence of biochemical abnormalities in the heterozygous individuals suggests that one normal allele is sufficient for secretion of intact FGF23

The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome

In type I blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), eyelid abnormalities are associated with ovarian failure. Type II BPES shows only the eyelid defects, but both types map to chromosome 3q23. We have positionally cloned a novel, putative winged helix/forkhead transcription factor gene, FOXL2, that is mutated to produce truncated proteins in type I families and larger proteins in type II. Consistent with an involvement in those tissues, FOXL2 is selectively expressed in the mesenchyme of developing mouse eyelids and in adult ovarian follicles; in adult humans, it appears predominantly in the ovary. FOXL2 represents a candidate gene for the polled/intersex syndrome XX sex-reversal goat