Silver-Russell syndrome – feeding, growth and metabolic risk
- Reference number
- UKR22-0072
- Project leader
- Muz, Nataliia
- Start and end dates
- 220601-231231
- Amount granted
- 1 000 000 SEK
- Administrative organization
- Göteborg University
- Research area
- Other
Summary
Main objectives - 50 children have been followed with the rare disease of the Silver-Russell syndrome from early childhood to adult life at the national centre of excellence at the Queen Silvia Children´s Hospital and in close collaboration with the University of Gothenburg. They have been extensively examined with endocrine evaluation and followed yearly with growth measures and sampling. Growth hormone has been given and pubertal development recorded. Working plan - All endocrine and growth data from patients with the diagnosis of Silver-Russell syndrome at Queen Silvia Children's Hospital (national and regional center) will be retrieved from the medical journals to make phenotypical mapping together with previous analyses of the genetic and epigenetic background. This study will be a part of a master study in Medicine 2022-23 supervised by the applicant. Steroid analyses will be performed at the lab of Göteborg Paediatric Growth Research Centre (GP-GRC). Data from the National Growth Hormone Registry for children in Sweden will be obtained in 2023. Two papers will be submitted to international journals.
Popular science description
The aim of this study is to improve the growth of children born with Silver-Russell syndrome (SRS). Based on a state of severe pre and postnatal growth retardation, they have a risk of severe short stature, type 2 diabetes and cardiovascular disease as adults. Today these children are treated with feeding tubes or surgery, but an increasing body of evidence points out that too little and too much is dangerous for metabolic health. Therefore 50 children have been followed with the rare disease of SRS from early childhood to adult life at the national centre of excellence at the Queen Silvia Children´s Hospital and in close collaboration with the University of Gothenburg. They have been extensively examined with endocrine evaluation and followed yearly with growth measures and sampling. Growth hormone has been given and pubertal development recorded. With me as a postdoc, I can gather these data and perform phenotype-genotype correlations. Specific research questions: 1. Feeding difficulties – is there a specific problem with the autonomic nerve system of the gastrointestinal tract leading to vomiting, swallowing problems, gastroesophageal reflux, obstipation, malrotation, leading to hypoglycemia, risk of malnutrition and severe low BMI during infancy and early childhood? 2. Early puberty – could early malnutrition and then later rapid weight gain induce a change in enzyme activity leading to early adrenarche and high estradiol levels in both genders? 3. Long-term outcome of GH treatment – could GH change the appetite and promote a rapid weight gain affecting BMI and adult height? Could then adding an aromatase inhibitor improve the outcome? Description of the strategic relevance of the proposed project: For the patients this project is of great importance in terms of avoiding type 2 diabetes, the metabolic syndrome (hypertension, dyslipidemia, insulin resistance, obesity) and cardiovascular disease in later life. The data will give us a clear response to the scientific questions and path the way for a more balanced treatment with individualized dosing of growth hormone, balanced nutrition for less visceral fat and lowering the risk for the metabolic syndrome. Based on the findings I can improve my care in Ukraine of the broader group children born intrauterine growth retarded as well as the more narrow group with Silver-Russell syndrome.