medwireNews: Growth hormone (GH) therapy in young children with Prader-Willi syndrome (PWS), genes linked to isolated short stature, and the role of insulin-like growth factor (IGF)-2 in autoimmune disease are the subjects of three papers included in the 2019 Yearbook of Paediatric Endocrinology.
In all, 14 papers have been included in the growth and growth factors chapter of the yearbook, Danilo Fintini (Bambino Gesù Children’s Hospital, Rome, Italy) told delegates at the 58th Annual ESPE Meeting in Vienna, Austria. He highlighted the findings of the three he believed were of greatest interest.
The most important for clinical practice was a study by Stephany Donze (Dutch Growth Research Foundation, Rotterdam, the Netherlands) and colleagues investigating the longer-term effects of growth hormone treatment on psychomotor development in very young children with PWS.
The study included 63 children (median age 1 year) with PWS who initiated GH treatment at a median of 1 year of age. At baseline, levels of mental and motor development, assessed using the Bayley Scales of Infant Development II, were 58.1% and 41.9% of those seen in healthy controls, respectively.
After 3 years of treatment, the mental and motor development levels among the children with PWS increased significantly to 79.6% and 78.2% of their healthy peers, respectively, and a younger age at treatment initiation was associated with a greater improvement in both outcomes.
The second paper Fintini presented was a multigene sequencing analysis of 55 children born small for gestational age (SGA) with isolated short stature. The analysis, by Bruna Friere (Universidade de Sao Paulo, Brazil) and team, identified eight heterozygous pathogenic or likely pathogenic variants in genes involved with growth disorders. These included growth plate genes (IHH, NPR2, SHOX, ACAN) and RAS/MAPK pathway genes (NF1, PTPN11).
None of the patients had a phenotype suggestive of a defective gene, and the authors therefore concluded that the identification of molecular aetiology of isolated short stature is important for providing a diagnosis to the patients and their families, to drive genetic counselling and for establishing the best therapeutic strategy.
The final paper, by Liming Du (Chinese Academy for Sciences, Shanghai) and co-researchers was highlighted as the “mechanism of the year” by Fintini.
Du and team investigated the anti-inflammatory actions of IGF-2 using an experimental autoimmune encephalomyelitis (EAE) model. They found that IGF-2 administration to human mesenchymal stem cells significantly lowered EAE clinical scores, was associated with reduced interleukin-1b and upregulated suppression of programmed cell death ligand 1 in maturing macrophages with persistent oxidative phosphorylation, and was able to modulate the innate immune memory of macrophages.
Summarising the three papers, Fintini said that “GH therapy in very young Prader-Willi children may improve mental and motor development, reducing the gaps between infants with and without PWS.”
He added: “Mild forms of skeletal dysplasia should be considered in SGA children with isolated short stature of unknown cause.”
And Fintini concluded that “IGF-2 may regulate [the] immune response system and may have a role in autoimmune diseases.”
By Laura Cowen
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