Shweta Namjoshi, MD

Abstract

Inherited syndromes of congenital enteropathy are rare, with many genetic causes described. Mutations of the AP1S1 gene results in the syndrome of intellectual disability, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma (IDEDNIK, formerly in the medical literature as MEDNIK). The clinicopathologic features of the enteropathy in IDEDNIK syndrome have not been fully explored. We describe a female infant who presented with metabolic acidosis, lethargy, and 14 watery stools per day. In the intensive care unit she required parenteral nutrition. She was found to have a novel homozygous pathogenic variant in the AP1S1 gene c.186T>G (p.Y62*). Esophagogastroduodenoscopy and colonoscopy at 6months of age were grossly normal. However, histologic sections of the duodenum showed mild villous blunting and enterocytes with cytoplasmic vacuoles. CD10 immunostaining highlighted the disrupted brush border. MOC31 immunostaining was wild-type with a membranous pattern of expression. Electron microscopy of the duodenum showed scattered enterocytes cells with shortened and disrupted apical microvilli. Although there is a mixed gap diarrhea and disrupted brush border, there are no significant inclusions typical of microvillus inclusion disease, nor tufted enterocytes typical of tufting enteropathy, making the clinical and histopathologic features for this syndrome unique.

View details for DOI 10.1177/10935266231177402

View details for PubMedID 37278357

Abstract

BACKGROUND: Pediatric patients with intestinal failure are at increased risk for iron deficiency. Supplementation is not routinely included in parenteral nutrition solutions. There is currently limited research related to the safety of iron supplementation in parenteral nutrition and for intravenous forms used in patients with intestinal failure. Current ASPEN and ESPGHAN guidelines promote the use of enteral iron, acknowledging the risks of using iron supplementation within parenteral nutrition admixtures.METHODS: We review a patient case and the current available literature related to iron in parenteral nutrition.RESULTS: Five major concerns are identified: peroxidation reactions, incompatibility, hypersensitivity, infection risk, and iron overload.CONCLUSION: We propose an argument against the preferential use of iron supplementation within parenteral nutrition in children with intestinal failure when enteral supplementation or intermittent parenteral infusion may be sufficient.CLINICAL RELEVANCY STATEMENT: Pediatric patients with intestinal failure are at risk for iron deficiency anemia, anemia due to folate or B12 deficiency, vitamin B6 deficiency, copper deficiency, non-anemic iron deficiency, and anemia of inflammation. Iron status assessment and supplementation for these patients is variable over time. There are several biochemical and physiologic concerns about the safety of adding iron supplementation to parenteral nutrition admixtures. This paper briefly reviews the current available literature. Further research is needed to evaluate best practices for iron supplementation for pediatric patients with intestinal failure. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/jpen.2428

View details for PubMedID 35730416

Abstract

Ferric citrate is approved as an iron replacement product in patients with non-dialysis chronic kidney disease and iron deficiency anemia. Ferric citrate-delivered iron is enterally absorbed, but the specific mechanisms involved have not been evaluated, including the possibilities of conventional, transcellular ferroportin-mediated absorption and/or citrate-mediated paracellular absorption. Here, we first demonstrate the efficacy of ferric citrate in high hepcidin models, including Tmprss6 knockout mice (characterized by iron-refractory iron deficiency anemia) with and without adenine diet-induced chronic kidney disease. Next, to assess whether or not enteral ferric citrate absorption is dependent on ferroportin, we evaluated the effects of ferric citrate in a tamoxifen-inducible, enterocyte-specific ferroportin knockout murine model (Villin-Cre-ERT2, Fpnflox/flox). In this model, ferroportin deletion was efficient, as tamoxifen injection induced a 4000-fold decrease in duodenum ferroportin mRNA expression, with undetectable ferroportin protein on Western blot of duodenal enterocytes, resulting in a severe iron deficiency anemia phenotype. In ferroportin-deficient mice, three weeks of 1% ferric citrate dietary supplementation, a dose that prevented iron deficiency in control mice, did not improve iron status or rescue the iron deficiency anemia phenotype. We repeated the conditional ferroportin knockout experiment in the setting of uremia, using an adenine nephropathy model, where three weeks of 1% ferric citrate dietary supplementation again failed to improve iron status or rescue the iron deficiency anemia phenotype. Thus, our data suggest that enteral ferric citrate absorption is dependent on conventional enterocyte iron transport by ferroportin and that, in these models, significant paracellular absorption does not occur.

View details for DOI 10.1016/j.kint.2021.10.036

View details for PubMedCentralID PMC8940695

View details for DOI 10.1007/s10620-022-07410-1

View details for PubMedID 35147818

View details for Web of Science ID 000707188005343

View details for Web of Science ID 000707188000205

View details for DOI 10.1097/PG9.0000000000000059

View details for PubMedID 34192292

View details for PubMedCentralID PMC8043327

Abstract

BACKGROUND: Glucose galactose malabsorption (GGM) is a congenital diarrheal disorder of intestinal Na+/glucose cotransport (SGLT1/SLC5A1). The required glucose and galactose-restricted diet has been well described in infancy, but long-term nutrition follow-up is limited.AIM: To perform a comprehensive nutritional assessment on a cohort of patients with GGM to gain insights into the consumption patterns within the population.METHODS: A cross-sectional study examining dietary intake of a GGM cohort using prospective food records. The calories and nutrients of all foods, beverages, and condiments were analyzed with descriptive statistics and compared to intake patterns of age- and sex-matched NHANES groups.RESULTS: The six patients were 0.7-26years old. Whole foods and vegetable fats were major parts of the diet, while dairy and added sweeteners were restricted. Compared to typical US intakes, mean macronutrient distribution was 88th percentile from fat, 18th percentile from carbohydrates, and 78th percentile from protein. Fructose consumption, as a proportion of total sugar intake, decreased with age, from 86.1 to 50.4%. Meanwhile, glucose consumption increased with age, from 13.8 to 48.6% of sugar intake. However, the actual amount of glucose consumed remained low, equivalent to 4th percentile of US consumption level. Galactose intake was marginal throughout life.CONCLUSIONS: A GGM diet is a high-fat and high-protein/low-carbohydrate diet that is rich in fruits and vegetables but limited in dairy and added sugar. Relatively less fructose but more glucose is incorporated into the diet with age. Future studies should investigate the effects of the GGM diet on gut microbiome and long-term health.

View details for DOI 10.1007/s10620-020-06792-4

View details for PubMedID 33433815

Abstract

Increased mortality risk due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry.In this multicenter observational cohort study, we collected data from 91 patients <21years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020.Patients with LD were more likely to require admission (70% vs 43% LT, p=0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, p=0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and one patient died. Bivariable logistic-regression analysis found that patients with non-alcoholic fatty liver disease (NAFLD) (OR 5.6, p=0.02) and LD (OR 6.1, p=0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death).Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

View details for DOI 10.1097/MPG.0000000000003077

View details for PubMedID 33605666

View details for DOI 10.1007/s42399-020-00404-y

View details for DOI 10.1097/PG9.0000000000000023

View details for DOI 10.1177/0148607117690528

View details for Web of Science ID 000425094500020