Endocrine Abstracts

JOINT1358

Introduction: Isolated growth hormone deficiency (IGHD) is a rare autosomal recessive disorder caused by mutations or deletions in the GH1 gene. It is characterized by early-onset severe short stature, extremely low levels of IGF-1, and a typical phenotype, including facial dysmorphism and genital abnormalities. IGF-1, a key mediator of growth hormone action, is critical for normal growth and development, and its deficiency leads to multisystemic consequences. Early genetic screening and treatment are essential to mitigate the impact of this condition on growth and overall health.

Case Presentation: This case study presents two siblings, aged 3 years and 7 months and 5 years and 10 months, diagnosed with severe growth deficiency and complex phenotypes. The consanguinity of their parents (second-degree cousins) and the family history, including an uncle with severe short stature (130 cm), suggest a significant genetic component. The phenotypes of the children were marked by facial dysmorphism (midfacial hypoplasia, hypoplasia of the nasal pyramid), micropenis (-3 DS), cryptorchidism, hypoplastic scrotum, and testicular hypotrophy. Both siblings presented with severe hypoglycemia at diagnosis (34 mg/dL and 25 mg/dL) and extremely low IGF-1 levels (<15 ng/ml and 26 ng/ml). Growth hormone therapy was initiated at different times, depending on the severity of their growth status. Somatropin treatment began 1 year and 9 months ago for both brothers. The older brother has shown a positive change in his growth trajectory, improving from -7.24 DS to -3.68 DS at present, while the younger brother has also demonstrated significant improvement, rising from -6.5 DS to -3.24 DS. Only the younger sibling has undergone genetic testing, which revealed a normal karyotype of 46,XY and a homozygous GH1 gene deletion was confirmed by WES.

Conclusions: This case highlights the importance of rigorous genetic and clinical monitoring in families with consanguinity. Differences in treatment timing and growth progression emphasize the phenotypic variability of growth hormone deficiency associated with the GH1 gene. Additionally, severe hypoglycemia and extremely low IGF-1 levels complete the multisystemic picture of this rare disorder.