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Silver-Russell syndrome - effect of nutrition on metabolism

Reference number
UKR24-0024
Project leader
Muz, Nataliia
Start and end dates
240501-251231
Amount granted
1 000 000 SEK
Administrative organization
Göteborg University
Research area
Other

Summary

The main objective is to conduct a comprehensive analysis of the phenotypic, molecular, metabolic and gastrointestinal aspects in adults with rare Silver-Russell Syndrome (SRS), and their impact on the quality of life. 86 individuals with SRS have been followed from childhood to adult life at the pediatric endocrine unit at Queen Silvia Children´s Hospital in Gothenburg in collaboration with Gothenburg University (GU) as the national center of reference for SRS. Recently data on clinical history, growth, treatments have been collected from medical journals. Gastrointestinal (GI) symptom rating scale questionnaires from 34 adults were obtained, indicating a high burden of symptoms. Working plan - clinical examination, gastroscopy, manometry in those with GI symptoms will be performed. Blood for biochemical and hormonal evaluation will be drawn including oral glucose tolerance test; methylation analysis will be conducted for 13 patients without known molecular cause. Body composition will be measured by dual-energy absorptiometry. Validated questionnaires will be used to study eating behavior, physical activity, quality of life, depression and work productivity. We expect to obtain the prevalence and manifestations of the metabolic syndrome (hypertension, dyslipidemia, insulin resistance, and obesity) and GI symptoms to elucidate how this correlates to quality of life and psychosocial functioning. More than 2-3 papers will be submitted to international journals.

Popular science description

Silver-Russell syndrome is a rare disorder, characterized by impaired growth and body composition. Each year, approximately two children with the rare Silver-Russell syndrome (SRS) are born in Sweden. The first international guideline for diagnosing and treating this syndrome was created in 2017. While we know a lot about the challenges during childhood, we have very little information about how it affects adults. In about two out of three people with Silver-Russell syndrome, there's a genetic cause. The most common genetic issues are a kind of loss of methylation on chromosome 11 (11p15 LOM), found in about half of the patients, or inheriting both chromosomes 7 from the mother and none from the father (maternal uniparental disomy 7), seen in around 10% of patients. Understanding these genetic factors helps us better grasp the roots of the syndrome, which is crucial for developing targeted ways to diagnose and treat it. We don't have much information about what happens to adults with SRS as they aren't regularly checked medically. This lack of follow-up means we don't know a lot about how SRS affects adults or the risk of gastrointestinal and metabolic problems. The aim of this study is to to conduct a comprehensive analysis of the phenotypic, molecular, metabolic and gastrointestinal aspects in adults with rare disorder SRS, and their impact on the quality of life. Therefore 30 individuals with SRS will be followed at the national center of excellence at the Queen Silvia Children´s Hospital and in close collaboration with the University of Gothenburg. We will gather detailed information about health history, including any activity and pain problems they've experienced. We'll look at growth charts over time, note any past and current treatments. Blood for biochemical and hormonal evaluation will be drawn including oral glucose tolerance test. Body composition will be measured by dual-energy absorptiometry. We'll also ask to answer some standardized questionnaires about eating habits, physical activity, quality of life, work productivity, and any challenges individuals with SRS may face in daily activities. The results from the study can then be used to develop treatment strategies and advice for people with SRS and their healthcare providers. In this way, the project can contribute to closing knowledge gaps in healthcare and improve the quality of life and health of people living with SRS.