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Background: Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8-10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking., Objective: Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data., Methods: This was a retrospective and prospective multicenter cohort study (2015-2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD., Results: We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (-44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal., Conclusion: Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed., Competing Interests: Declaration of competing interest • NP has received honoraria from ADEN-ALLP, Alexion AMGEN, Amryt, Biocodex, Elsevier, Kowa, Lactalis, Nestlé NHS, NHC, Nutricia-Danone, Orphan Europ, Sanofi, Shire, Ultragenyx • PT has participated in one scientific committee at Ultragenyx laboratories • YP has received honoraria from Servier, Viatris, AMGEN, Sanofi, Bouchara-Recordati • JPR has received remuneration from Sanofi, Ultragenyx • EB has received honoraria from AstraZeneca, AMGEN, MSD, Sanofi and Regeneron, Aegerion/Amryt, Lilly, Ionis-pharmaceuticals, Akcea, Alexion pharma, Servier, Novartis, Mylan/Viatris, Organon and Genfit • AG reports grants and personal fees from AMGEN, Sanofi, Regeneron, Mylan Viatris, MSD, Akcea Therapeutics, Amryt and Ultragenyx. • SB has received honoraria for board, conferences, clinical trial or congress from Aegerion, Akcea, Elivie, Novartis, Sanofi or AMGEN • PP, LR, AV, RR have no conflict of interest related to this article., (Copyright © 2024 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

The role of nutritional interventions for the primary prevention of cow's milk allergy (CMA) remains debated as well as the role of early introduction of allergenic foods, which is largely encouraged from the beginning of complementary feeding. Considering the introduction of cow's milk protein (CMP), current recommendations suggest avoidance of any cow's milk formula (CMF) supplements in breastfed infants in the maternity ward. By contrast, based on poor evidence, some authors support systematic supplements of CMP in breastfed children at risk of allergy from the first week of life. The Committee on Nutrition of the French Society of Pediatrics considers that such a proposal requires more clinical studies and mainly randomized and placebo-controlled clinical trials before becoming a recommendation., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest with this work. The authors did not receive any financial support for this work., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals., (Copyright © 2022. Published by Elsevier Inc.)

Congenital diarrhea may result from 2 main different mechanisms: 1) osmotic diarrhea is caused by the non-digestion-absorption of nutrients leading to the non-absorbed nutrients going into the lumen, increasing the osmotic force and driving fluids; 2) secretory diarrhea induced by the inhibition of intestinal absorption of electrolytes, increasing electrolyte and water flux towards the intestinal lumen. The malabsorption of macronutrients (carbohydrates, proteins and lipids) induces energy deficiency with symptoms depending on the macronutrient: carbohydrates with watery acidic diarrhea; protein with rapid malnutrition, edema, and hypoalbuminemia; and lipids with malnutrition, steatorrhea and hypocholesterolemia. Ionic malabsorption (Cl and Na) is responsible for severe and rapid dehydration sometimes with prenatal abnormalities (polyhydramnios and bowel dilatation)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aims: Home Parenteral Nutrition (HPN) is the cornerstone management for children suffering from chronic intestinal failure (CIF). In France, HPN is organized from a network of 7 certified centers located in University Hospitals spread across the national territory. This study aims to review the data involving children on HPN over a 6-years period in France to outline the global and continuous improvement in care., Patients and Methods: This cross-sectional study included all children enrolled in any of the 7 French HPN certified centers from January 1st, 2014 to December 31st, 2019. Data was recorded from annual databases provided by each center regarding: age at inclusion, indication and duration of HPN, type of intravenous lipid emulsion (ILE), outcome [PN weaning off, transfer to adult center, death, intestinal transplantation (ITx)], rate of catheter-related bloodstream infections (CRSBIs) for 1000 days of HPN, Taurolidine lock procedure (TLP) use and prevalence of cholestasis defined as conjugated bilirubin ≥20 μmol/l., Results: The number of patients increased by 43.6% from 268 in 2014 to 385 in 2019. According to the year of follow up, the indications for HPN were short bowel syndrome (SBS) (42.3-46.6%), congenital enteropathies (CE) (18.5-22.8%), chronic intestinal pseudo-obstruction syndrome (CIPOS) (13.0-16.3%), long segment Hirschsprung's disease (LSHD) (9.7-13.3%), Crohn's disease (CD) (1.6-2.6%) and other non-primary digestive diseases (NPDD) such as immune deficiency, cancer or metabolic disease (4.0-9.2%). The median age at discharge on HPN decreased from 11.7 months in 2014 to 8.3 months in 2019 (p < .001). By December 31st, 2019, 44.8% of children had left the HPN program after a median duration ranging between 39.9 and 66.4 months. Among these patients, 192 (74.2%) were weaned off PN (94.7% SBS), 41 (15.8%) were transferred to adult centers for CIPOS (42%), SBS (31%) or CE (27%), 21 died (8.1%) - mostly in relation to cancer or immune deficiency - and 5 were transplanted (1.9%): 4 underwent combined liver-intestine transplantation for LSHD (n = 2), SBS, CE and one multivisceral Tx for CIPOS. The use of a composite fish-oil based ILE increased from 67.4% in 2014 to 88.3% in 2019 (p < 0.001). CRBSIs dropped from 1.04 CRSBIs per 1000 days HPN in 2014 to 0.61 in 2019 (p < 0.001) while meantime, the percentage of children receiving TLP increased from 29.4% to 63.0% (p < 0.001). The prevalence of cholestasis (conjugated bilirubin ≥ 20 μmol/l) was low and stable between 4.1 and 5.9% of children during the study period., Conclusion: In France, the number of children enrolled in a HPN program continuously increased over a 6 years period. SBS is the leading cause of CIF requiring HPN. The rate of CRBSIs dropped dramatically as the use of TLP increased. Mortality rate was low and mainly in relation to the underlying disease (cancer, immune deficiency). Cholestasis and intestinal Tx remained very rare., Competing Interests: Conflict of interest The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Chylomicron retention disease (CRD) is an autosomal recessive disorder associated with biallelic Sar1b mutations leading to defects in intracellular chylomicron (CM) trafficking and secretion. To date, a direct cause-effect relationship between CRD and Sar1b mutation has not been established, but genetically modified animal models provide an opportunity to elucidate unrecognized aspects of these mutations. To examine the physiological role and molecular mechanisms of Sar1b function, we generated mice expressing either a targeted deletion or mutation of human Sar1b using the CRISPR-Cas9 system. We found that deletion or mutation of Sar1b in mice resulted in late-gestation lethality of homozygous embryos. Moreover, compared with WT mice, heterozygotes carrying a single disrupted Sar1b allele displayed lower plasma levels of triglycerides, total cholesterol, and HDL-cholesterol, along with reduced CM secretion following gastric lipid gavage. Similarly, decreased expression of apolipoprotein B and microsomal triglyceride transfer protein was observed in correlation with the accumulation of mucosal lipids. Inefficient fat absorption in heterozygotes was confirmed via an increase in fecal lipid excretion. Furthermore, genetically modified Sar1b affected intestinal lipid homeostasis as demonstrated by enhanced fatty acid β-oxidation and diminished lipogenesis through the modulation of transcription factors. This is the first reported mammalian animal model with human Sar1b genetic defects, which reproduces some of the characteristic CRD features and provides a direct cause-effect demonstration., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The childhood/adult-onset lysosomal acid lipase deficiency (LALD; late-onset LALD) is a rare genetic disease. Children present severe fatty liver disease with early cirrhosis. Before enzyme replacement therapy, statins were the standard treatment to improve the severe dyslipidemia. However, late-onset LALD should be considered as a systemic metabolic disease: chronic hyper-low-density lipoprotein and hypo-high-density lipoprotein cholesterolemia induces early atherosclerosis in addition to the liver morbidity., Objective: To assess 4 new pediatric cases of late-onset LALD with an evaluation of hepatic, metabolic, and vascular evolution under statin., Methods: Four patients were retrospectively described. Anthropometric data (weight, height, and body mass index) and laboratory data (LIPA mutations, acid lipase residual activity, liver and lipid profile, and homeostatic model assessment index) were collected. Liver histology was assessed by the noninvasive tests FibroScan and FibroTest and confirmed by liver biopsy. Vascular impact was followed up by carotid intima-media thickness (cIMT) assessment., Results: The 4 cases of late-onset LALD came from 2 families, each with a boy (aged 8.6 and 11 years at diagnosis) and a girl (aged 10.6 and 13 years at diagnosis). Treatment with statins was performed for 8 and 5 years, respectively, from diagnosis. Statins decreased the low-density lipoprotein cholesterol mean value of 40%. All children showed significant liver fibrosis (F3 [n = 3]; F2 [n = 1]). cIMT showed the following for all children: abnormal measures without improvement and atherosclerotic plaques. One child developed a deleterious metabolic phenotype with obesity and insulin resistance (homeostatic model assessment = 3.08) associated with higher mean hepatic transaminases (149 vs 98, 88, and 61 IU/L) and increased mean cIMT values (raising from 0.47 to 0.5 mm vs 0.43 and 0.43 mm)., Conclusion: Late-onset LALD is a rare metabolic disease with a larger impact than liver disease. Our work shows the importance of having a global metabolic view and to evaluate the cardiovascular impact of the new enzymatic treatment., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background & Aims: This retrospective study evaluated the impact of new organization during the moving to a new university pediatric hospital on the incidence of central catheter-related blood stream infections (CRBSIs) among children on long-term parenteral nutrition., Methods: The study ran from April 2007 to March 2014, starting a year prior to reorganisation of the department of pediatric Hepato-Gastroenterology and Nutrition associated to moving the children to a new hospital in April 2008, and continuing for 6 years following the move. During this time, data from all children hospitalized in this department who received parenteral nutrition (PN) for more than 15 days were analysed., Results: During this 7-years study, 183 children aged 4.6 ± 0.5 years received prolonged PN. Intestinal diseases were the main aetiologies (89%), primarily short bowel syndrome (18.4%), Hirschsprung disease and CIPO (13.5%) and inflammatory bowel disease (13.8%). The mean durations of hospitalization and of PN during hospitalization were, respectively, 70 ± 2.1 and 55.7 ± 3.6 days. During the study period, 151 CRBSIs occurred in 77 children (42% of all patients), i.e. 14.8 septic episodes/1000 PN days and 12.0 septic episodes/1000 CVC days. No patient died of a central venous catheter-related infection. However, following the move from the older hospital to the newer one, the rate of CRBSIs significantly doubled, from 3.9/1000 to 8.8/1000 CVC days (p = 0.02). During the following 4 years, the incidence of CRBSIs tended to increase between the 2nd and the 5th year after the move: 11.3 (p = NS); 21.4 (p = 0.01); 17.3 (p = NS), 20.3/1000 (p = NS) CVC days. We also observed that after evaluations by the Department of Infection Control, nurse training and stabilization of the nursing team, the incidence decreased significantly from 20.3 to 11.1/1000 CVC days during the 6th year after the move (p = 0.01)., Conclusion: Our results reveal the deleterious impact of the reorganization during the hospital moving on the CRBSI incidence rate, and the possible implication of inexperienced team of nurses., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)