ESPE Abstracts

Background: We present the case of a 7.5-year-old male of Sephardic Jewish descent, born to non-consanguineous parents, diagnosed with Hemophilia B and a SOX3 gene deletion. The child exhibited endocrine disorders and developmental delay.

Case Presentation: Born full-term following an uncomplicated pregnancy, he was diagnosed with Hemophilia B shortly after birth due to a significant hemorrhage post-routine dextrose check and the development of severe cephalohematoma. Subsequently, he received recombinant factor IX therapy and has been under hematology surveillance since. At 4.4 months, he presented to the pediatric endocrinology unit at Sheba Hospital with morbid obesity (weight: 10.6 kg, WHO SDS +3.58) and abnormal thyroid function tests (TSH: 7.8 mIU/L, FT4: 7 pmol/L), leading to the initiation of Euthyrox treatment, which was later discontinued at age three. Additionally, he exhibited delayed speech and motor development and began walking at 1.9 years of age.

Genetic Analysis: Sanger sequencing of the F9 gene uncovered complete gene deletion on the X chromosome. Subsequent exome sequencing revealed a deletion encompassing the F9, SOX3, ATP11C, and FGF13 genes. His mother tested negative for these genetic changes. The SOX3 gene is integral to the development of the pituitary, brain, and facial structures. SOX3 mutations are associated with a spectrum of phenotypes, including hypopituitarism, isolated GH deficiency, intellectual disability, severe early childhood obesity and craniofacial anomalies. Phenotypic expression varies significantly, even among individuals with the same mutation.

Endocrine Evaluation: Despite maintaining growth at the 40^th percentile, a clonidine stimulation test was conducted to assess the GH axis, yielding a flat response with a peak GH level of 1.6 μg/L, indicative of GH deficiency. Therefore, GH therapy was initiated at the age of 5 years.

Outcomes: Following GH therapy, the patient demonstrated a notable improvement in growth velocity, ascending to the 80^th percentile. BMI SDS was reduced from +3.5 to +2.2 over a two-year period. Additionally, there was a decrease in hyperphagia and food-seeking behaviors reported by the parents.

Conclusion: This case highlights the potential benefits of GH therapy in pediatric patients with SOX3 mutation, showing substantial improvements in growth and anthropometric measures. Further research is needed to optimize GH therapy and understand its long-term effects in similar genetic contexts.