ESPE Abstracts

Introduction: The PAPPA2 gene plays a crucial role in growth regulation through its interaction with the insulin-like growth factor (IGF) system. Mutations in this gene can lead to disrupted growth patterns. This case report describes the clinical course of a Yemeni girl with a pathogenic PAPPA2 variant, characterized by high IGF-1 levels and affected linear growth and weight gain.

Case Presentation: A 5-year-old girl of Yemeni descent, born preterm at 35 weeks with intrauterine growth restriction (IUGR), presented with failure to thrive and short stature. Initially, her measurements were significantly below the mean for her gestational age, with a birth weight of 1.7 kg (-3.7 SDS), length of 45 cm (-1.7 SDS), and head circumference of 42 cm (-2 SDS). Despite normal metabolic, immunological, and gastrointestinal function tests, her growth remained stunted. Whole exome sequencing identified a homozygous pathogenic variant in the PAPPA2 gene. Nutritional interventions led to intermittent improvements in growth metrics. However, discontinuation of a high-calorie, high-protein diet resulted in a decline in her growth velocity, which was later restored with oral nutritional supplementation.

Results: The patient showed marked fluctuations in weight and height standard deviation scores (SDS) and growth velocity (GV) over time, with notable decreases during periods of inadequate nutrition. The Introduction of a high-calorie, high-protein diet through nasogastric tube (NGT) feeding initially improved weight and growth velocity, but the cessation of this diet led to negative growth outcomes. Reinitiation of oral nutritional supplements corresponded with improvements in growth parameters and IGF-1 levels, although these remained above average.

Conclusion: This case underscores the importance of nutritional management in patients with growth disorders associated with PAPPA2 mutations. It highlights the complexities of growth regulation in the context of genetic abnormalities and the potential reversibility of growth deficits with appropriate interventions. Regular follow-up and adherence to nutritional guidelines are imperative for managing similar cases.