Down Syndrome and Pediatric Nonalcoholic Fatty Liver Disease: A Causal or Casual Relationship?

Matteo, Antonia De; Vajro, Pietro

doi:10.1016/j.jpeds.2017.07.011

Cited by 10 publications

(9 citation statements)

References 40 publications

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“…Body mass index was associated with increases in GGT in children, and with increases in AST and total protein levels in adults. This study adds to prior findings of an increased risk for liver dysfunction during in children with DS (de Matteo & Vajro, 2017; Valentini et al, 2017, 2020), while our finding in adults suggest that adiposity‐associated liver disease may represent a life‐course process in individuals with DS.…”

Section: Discussionsupporting

confidence: 82%

Cardiometabolic profiles in children and adults with overweight and obesity and down syndrome

Oreskovic

Baumer

Camillo

et al. 2022

American J of Med Genetics Pt A

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Individuals with Down syndrome (DS) are at increased risk for being overweight/obese, but the associated cardiometabolic risk (CR) is not clear. Cross‐sectional anthropometric and clinical laboratory data from a multi‐site, international cohort of individuals with DS were analyzed to determine cardiometabolic risk by reporting observed distributions of cardiometabolic biomarkers in overweight/obese individuals with DS throughout the lifespan. Descriptive statistics and regression analyses by age categories determined the distributive percentiles for cardiometabolic biomarkers and tested for adiposity as a predictor of CR. Across seven DS clinics, data were collected on 240 patients between the ages of 3 and 63 years, with one quarter overweight and three quarters obese among children and nearly all adults being obese. In children and adults, most cardiometabolic biomarker profiles showed distributive values within normal ranges. Blood lipids were positively associated with body mass index (BMI) in children (high density lipid‐cholesterol, p = 0.01; low density lipid‐cholesterol, p = 0.02). Levels of hs‐CRP were elevated in both children and adults, with BMI positively associated with hs‐CRP in adults with DS (p = 0.04). Liver enzyme values were positively associated with BMI in children and adults. The data suggest that in contrast to the general population, in individuals with Down syndrome, being overweight and obese does not appear to confer a significantly increased risk for cardiometabolic disease by biomarker profile. Individuals with DS who are overweight/obese appear to have unique cardiometabolic profiles unrelated to adiposity, notable for increased hs‐CRP and normal HA1c levels.

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Section: Discussionsupporting

confidence: 82%

Cardiometabolic profiles in children and adults with overweight and obesity and down syndrome

Oreskovic

Baumer

Camillo

et al. 2022

American J of Med Genetics Pt A

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“…They demonstrated that, independently from the obese phenotype, children and adolescents with DS display a greater risk to develop nonalcoholic fatty liver disease than the general pediatric population (Valentini et al, ). An elevated incidence of hepatic steatosis detected by histological evaluation in patients with DS (63%), twice as high as that seen in other intellectually deficient controls had already been reported in the first half of the last century (De Matteo & Vajro, ). In our patients, the frequency was lower, but they were screened only by ultrasound.…”

Section: Discussionmentioning

confidence: 53%

Gastrointestinal disorders in Down syndrome

Bermudez

Oliveira

Cat

et al. 2019

American J of Med Genetics Pt A

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Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10-year follow-up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow-up as well as adequate development and greater quality of life for patients with Down syndrome and their families. K E Y W O R D S congenital malformation, Down syndrome, gastrointestinal diseases

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“…This has been commonly attributed to the fact that DS individuals perform less physical activity and perhaps to different dietary habits (Hawli et al 2009 ; Bala et al 2018 ; Dupre and Weidman-Evans 2017 ; González-Agüero et al 2011 ). Moreover, various lines of biochemical and endocrinology investigations, demonstrating increased adipokine production, altered lipid handling, subchronic inflammation, subclinical or manifest insulin resistance and/or metabolic syndrome (Magni et al 2004 ; Corsi et al 2009 ; de Asua et al 2014a , b ) and the development of fatty liver (Seeff et al 1967 ; De Matteo and Vajro 2017 ) point to intrinsic biochemical differences in the development of obesity in DS.…”

Section: Down Syndrome As a Metabolic Disease: An Introductionmentioning

confidence: 99%

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

Pecze

Randi

Szabó

2020

Mol Med

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Clinical observations and preclinical studies both suggest that Down syndrome (DS) may be associated with significant metabolic and bioenergetic alterations. However, the relevant scientific literature has not yet been systematically reviewed. The aim of the current study was to conduct a meta-analysis of metabolites involved in bioenergetics pathways in DS to conclusively determine the difference between DS and control subjects. We discuss these findings and their potential relevance in the context of pathogenesis and experimental therapy of DS. Articles published before July 1, 2020, were identified by using the search terms “Down syndrome” and “metabolite name” or “trisomy 21” and “metabolite name”. Moreover, DS-related metabolomics studies and bioenergetics literature were also reviewed. 41 published reports and associated databases were identified, from which the descriptive information and the relevant metabolomic parameters were extracted and analyzed. Mixed effect model revealed the following changes in DS: significantly decreased ATP, CoQ10, homocysteine, serine, arginine and tyrosine; slightly decreased ADP; significantly increased uric acid, succinate, lactate and cysteine; slightly increased phosphate, pyruvate and citrate. However, the concentrations of AMP, 2,3-diphosphoglycerate, glucose, and glutamine were comparable in the DS vs. control populations. We conclude that cells of subjects with DS are in a pseudo-hypoxic state: the cellular metabolic and bio-energetic mechanisms exhibit pathophysiological alterations that resemble the cellular responses associated with hypoxia, even though the supply of the cells with oxygen is not disrupted. This fundamental alteration may be, at least in part, responsible for a variety of functional deficits associated with DS, including reduced exercise difference, impaired neurocognitive status and neurodegeneration.

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Down Syndrome and Pediatric Nonalcoholic Fatty Liver Disease: A Causal or Casual Relationship?

Cited by 10 publications

References 40 publications

Cardiometabolic profiles in children and adults with overweight and obesity and down syndrome

Cardiometabolic profiles in children and adults with overweight and obesity and down syndrome

Gastrointestinal disorders in Down syndrome

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

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