PSAT105 Evaluation of Body Mass Index and Metabolic Parameters in Children with Achondroplasia Participating in the PROPEL Study

Abstract Background Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia, affecting between 1 in 15,000 to 1 in 30,000 live births. Children and adults with ACH have disproportionate short stature and are at risk for several significant co-morbidities, including obstructive sleep apnea, chronic otitis media with conductive hearing loss, and spinal stenosis. Obesity is a health problem in ACH and aggravates breathing difficulties (i.e. sleep apnea), back and joint pain, and reduced mobility. Individuals with ACH are predisposed to abdominal obesity, although the cause is not completely understood. The metabolic effect of visceral obesity does not suggest an association with the development of a diabetic profile. The objective of this study is to evaluate body mass index (BMI) and metabolic parameters in children with ACH participating in the PROPEL study, a prospective, non-interventional study designed to examine baseline growth parameters and health status in children being assessed for potential enrollment into interventional studies with infigratinib, an oral FGFR1–3 inhibitor in development for ACH. Methods Data were analyzed from 86 children (mean age 6.1±2.5 years; female n=52) enrolled in PROPEL. BMI was calculated at enrollment and compared with sex- and age-specific BMI curves for children with ACH in the United States. Cholesterol, triglycerides, and hemoglobin A1c were measured centrally in a subset of children. Results BMI (mean±SD) was 21.2±2.2 in females (range 16.8–26.2) and 20.5±1.6 in males (range 17.9–24.6), with 8/52 girls (15%) and 1/34 boys (2.9%) presenting BMI above the 95% of the sex- and age-specific BMI curves for ACH. The mean±SD for cholesterol and triglycerides measured in a subset of 43 children were 4.2±0.7 mmol/L (normal range [NR] 2.59–4.66) and 0.9±0.5 mmol/L (NR 0.56–1.36), respectively. Cholesterol was elevated in 9/43 children (20.9%), while triglycerides were high in 8/43 (18.7%). Hemoglobin A1c (HbA1c) was measured in 28 children and had a mean±SD of 0.052±0.002 (NR Hb fraction 0.04–0.06). Although all values were within normal ranges, 19/28 (68%) of children had values above the mean for laboratory reference values. Conclusion Results from this work illustrate the importance of using BMI tables developed for children with ACH when providing guidance on weight management. Furthermore, our findings suggest that, in this cohort, average cholesterol and HbA1c levels, although normal, are above the mean for the reference population; this highlights the importance of a healthy diet, weight management and regular physical activity starting at young age. Additional studies are needed to understand the relationship between BMI and body composition in individuals with short stature and to further investigate the clinical relevance of these findings given that no association between increased BMI and metabolic syndrome has been described in adults with ACH. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.