Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor

Background - Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental syndrome with highly increased risk of obesity and cardiovascular disease (CVD). Recent evidence suggests that inflammation is implicated in the pathogenesis. Here we investigated CVD related immune markers to shed light on pathogenetic mechanisms. Methods - We performed a cross-sectional study with 22 participants with PWS and 22 healthy controls (HC), and compared levels of 21 inflammatory markers that reflect activity in different aspects of CVD related immune pathways and analyzed their association with clinical CVD risk factors. Results - Serum levels of matrix metalloproteinase 9 (MMP-9) was (median (range)) 121 (182) ng/ml in PWS versus 44 (51) ng/ml in HC, p = 1 × 10-9), myeloperoxidase (MPO) was 183 (696) ng/ml versus 65 (180) ng/ml, p = 1 × 10-5) and macrophage inhibitory factor (MIF) was 46 (150) ng/ml versus 121 (163) ng/ml (p = 1 × 10-3), after adjusting for age and sex. Also other markers tended to be elevated (OPG, sIL2RA, CHI3L1, VEGF) but not significantly after Bonferroni correction (p > 0.002). As expected PWS had higher body mass index, waist circumference, leptin, C-reactive protein, glycosylated hemoglobin (HbA1c), VAI and cholesterol, but MMP-9, MPO and MIF remained significantly different in PWS after adjustment for these clinical CVD risk factors. Conclusion - PWS had elevated levels of MMP-9 and MPO and of reduced levels of MIF, which were not secondary to comorbid CVD risk factors. This immune profile suggests enhanced monocyte/neutrophil activation, impaired macrophage inhibition with enhanced extracellular matrix remodeling. These findings warrant further studies targeting these immune pathways in PWS

Nutritional challenges in children and adolescents with Down syndrome

Several features and comorbidities in Down syndrome have nutritional implications and consequences. In infancy and early childhood, children with Down syndrome have a high risk of oral motor difficulties and pharyngeal dysphagia with aspiration, which both require systematic attention. To improve nutritional status in children who are underweight and who have clinical signs of feeding problems, further evaluation of underlying causes is required. Clinical interventions should promote swallowing safety and development of feeding abilities. Even from 4–5 years of age, overweight in children with Down syndrome can be a concern. To prevent disease later in life, an urgent need exists for more research on nutritional aspects in the prevention and treatment of obesity in adolescents with Down syndrome. This Review did not find any data to support the use of dietary supplementation, except when deficiency is documented. Additionally, the literature reported the need for more research that uses larger study samples and control groups and that addresses important nutritional challenges in children and adolescents with Down syndrome

Dietary aspects related to health and obesity in Williams syndrome, Down syndrome, and Prader–Willi syndrome

Background: Dietary aspects that might contribute to development of obesity and secondary conditions are not well documented in genetic subgroups associated with intellectual disability. Objective: To describe the intake frequencies of selected foods in participants with Prader–Willi syndrome (PWS), Down syndrome (DS), and Williams syndrome (WS), and investigate the association with body mass index (BMI). To explore food-related autonomy and intake frequencies among persons with DS in different living arrangements. Methods: Self-reported intake frequencies and measurement of plasma carotenoids and erythrocyte content of omega-3 fatty acids (FAs) were investigated in persons aged 16–42 years, with WS (n=21), DS (n=40), and PWS (n=20). Results: A larger proportion of participants with PWS showed high-frequency intake of fruits (p=0.012) and vegetables (p=0.004), and had higher plasma carotenoids (p<0.001) compared to participants with DS and WS. Furthermore, a larger proportion of participants with WS were low-frequency consumers of fish (p=0.005), less likely to use omega-3 FA supplements (p=0.023), and had reduced erythrocyte concentrations of long-chain omega-3 FAs (p<0.001), compared to participants with PWS and DS. In DS, BMI was negatively associated with plasma carotenoids. Increased proportions of participants living in communities showed high-frequency intake of precooked meals (p=0.030), and a tendency toward high-frequency consumption of soft drinks (p=0.079), when compared to peers living with relatives. Participants in community residences were also more likely to participate frequently in food-related decisions and preparations. Conclusions: Persons with WS had a less-favorable dietary pattern when compared to persons with PWS. A larger proportion of persons living in communities frequently consumed precooked meals and showed a tendency of high-frequency soft drink consumption. Otherwise, their intake frequencies of the investigated foods were similar to those living with relatives, but they participated more frequently in decisions and preparations of foods

Factors influencing the opportunities of supporting staff to promote a healthy diet in adults with intellectual disabilities

Background Adults with intellectual disabilities living in residential houses have a high prevalence of obesity which is related to poor dietary habits. Aim The aim of this study was to assess supporting staff`s thoughts and experiences on factors influencing their opportunities to promote a healthy diet in adults with intellectual disabilities. Methods 13 supporting staff members were recruited from 11 different residential houses in a community. Concept Mapping methodology was used, including group interviews, sorting, rating statement and analysing the results. Results Seven clusters most accurately captured the ideas of the supporting staff`. ‘Attitudes’, ‘Facilitating a healthy diet’, ‘Practical cooking skills’ and ‘Applied dietary knowledge’ were the four most important. Conclusions Multiple factors influence the opportunities of supporting staff to promote a healthy diet. A holistic approach addressing all relevant factors is necessary when developing interventions to address this complex issue in persons with intellectual disabilities

Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome

In this study we describe by use of accelerometers the total physical activity (PA), intensity pattern and walking capacity in 87 persons age 16–45 years with Down syndrome (DS), Williams syndrome (WS) and Prader–Willi syndrome (PWS). Participants were recruited from all over Norway, and lived either with their parents or in community residences with support. On average the participants generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71 min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic recommendations for PA. When compared, no differences for total physical activity or time in MVPA were observed between the three groups. However, participant with DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities compared to participants with PWS and WS, respectively, (p = 0.011, 95% CI: −10.9; −80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than the PWS-group and 41 min/day more than the WS-group, (p < 0.001, 95% CI: 29.3; 79.7). Participants with PWS spent on average 30 min/day less in lifestyle activities compared to both participants with DS and WS, (p < 0.001, 95% CI: −14.2; −45.4). No association between total PA and BMI were observed. Males were more active than females across all diagnoses. Males accumulated on average 85 counts per minutes more than females, (p = 0.002, 95% CI: 33.3; 136.7), 2137 more steps per day, (p = 0.002, 95% CI: 778; 3496). The mean walking capacity during six-minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance walked during testing decreased with 33.6 m when comparing normal or underweight participants to overweight participants, and 78.1 m when comparing overweight to obese participants (p < 0.001 95% CI: −40.4; −85.8). When adjusted for BMI no differences in walking capacity between the three genetic conditions were observed

Securing rights and nutritional Health for persons with intellectual disabilities - a pressing challenge

Persons with intellectual disabilities (ID) are dependent on nutritional policies that have so far not been addressed in a systematic and health-promoting manner in Norway and other nations with a high socioeconomic standard. In many poor countries, such issues have not even been raised nor addressed. Nutritional issues facing persons with ID include the risk of both underweight and overweight. Deficiency in energy, vitamins, essential fatty acids and micronutrients can increase the risk of additional health burdens in already highly vulnerable individuals. According to the World Health Organization, the obesity rates have tripled worldwide the last decades, and recent studies suggest that the prevalence of obesity is even higher for persons with ID than in the general population. This implies additional burdens of life style diseases such as diabetes and hypertension for adults with ID. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5, this group is characterized by intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Their reduced intellectual capacity implies that they often have difficulties in making good dietary choices. As a group, they are dependent upon help and guidance to promote a healthy life style. To improve their health, there is a need for improved national services and for more research on lifestyle and nutritional issues in persons with ID. From a human rights perspective, these issues must be put on the agenda both in relevant UN fora and in the respective nations’ health policies

Weight reduction and dietary improvements in a cluster-randomised controlled trial for adults with intellectual disabilities

Background: People with intellectual disabilities (IDs) have an increased risk of obesity and health concerns related to their nutritional status and dietary intake. Objective: To assess the effectiveness of a multi-component intervention on weight, waist circumference (WC), clinical health parameters and dietary habits in a group of overweight and obese adults with mild-to-moderate ID. Design: A 7-month cluster-randomised trial and a 7-month follow-up of the intervention group after the end of intervention when the group received usual care. The intervention consisted of monthly dietary-group courses tailored to the participants’ cognitive abilities and practical skills, monthly nutritional courses for staff, use of behaviour change techniques and nudging. The control group received usual care during the intervention. Results: There were 32 participants aged 22–61 years: 15 in the intervention group and 17 in the control group. After 7 months, a non-significant weight difference (median difference = −1.25 kg; 95% confidence interval [CI] = −2.00; 0.95 vs. +1.00 kg; CI = −1.15; 3.00, P = 0.08) and a significant WC difference were observed between the intervention and control groups (median difference = −3.75 cm; CI: −7.68; 0.11 vs. 0 cm; CI = −3.99; 1.00, P = 0.03), respectively. The median reduction in WC continued in the intervention group during the 7-month follow-up (median difference = −7.50 cm; CI: −13.57; −3.16, P = 0.002). A significant difference in frequency intake of fruit (P = 0.03) and berries (P = 0.004) was observed between the groups after 7 months, supported by a significant increase in measured serum-carotenoid levels in the intervention group after 7 months (median difference = 0.26 mmol/L; CI: −0.12; 0.52, P = 0.007). Conclusions: A significant difference in WC was observed between the groups, accompanied by changes in blood parameters and dietary habits

Nutritional status and dietary intake in children and adolescents with spinal muscular atrophy types II and III on treatment with nusinersen

Summary: Background: There are few assessments of nutritional care needs of children and adolescents with spinal muscular atrophy (SMA) after disease-modifying treatments became available. Aims: To assess nutritional status, dietary intake and feeding difficulties in children and adolescents with SMA II and SMA III on treatment with nusinersen, and to explore possible associations between feeding difficulties and dietary intake. Methods: Nutritional status was assessed by anthropometric measures and blood samples from annual follow-up appointments over a three-year period. Three 24-hour dietary recalls by phone were used to assess dietary intake. Feeding difficulties were assessed by the Egen Klassifikation- 2 scale. Results: This study included 20 participants with SMA II with a median age of 7.0 (Q1 2.0; Q3 12.9) years and 20 participants with SMA III with a median age of 8.4 (Q1 4.3; Q3 12.2) years. Adequate intake of iron and vitamin D was dependent on use of supplementation. Iron deficiency was implied in 17.5 %, whereas vitamin D deficiency was documented in 5 % and vitamin D insufficiency in 37.5 % of the total SMA cohort. Growth failure with small mean decrease in height-for-age z-score over time was observed in both subgroups, however only significant in the SMA II group (P=0.02). Feeding difficulties were associated with reduced intake of protein -4.6 grams per day, 95 % CI [-7.3; -1.8], P=0.002. Conclusions: Systematic monitoring of nutritional status continues to be important in pediatric patients with SMA II and SMA III on disease-modifying treatment. Attention in clinical care should be on prevention and treatment of nutritional deficits, with emphasis on iron and vitamin D status and adequate protein intake in persons with feeding difficulties