Novel compound heterozygous mutations in the SBP2 gene: Characteristic clinical manifestations and the implications of GH and triiodothyronine in longitudinal bone growth and maturation

Objective: Mutations in the selenocysteine insertion sequence binding protein 2 gene (SECISBP2 also known as SBP2) lead to a multisystemic disorder. Our objectives are to examine the clinical manifestations of the present patient and evaluate the effects of GH and triiodothyronine (T ₃) for longitudinal bone growth and maturation. Methods: A Japanese boy presented with unusual thyroid function tests (normal or slightly elevated TSH, low-normal or slightly decreased free T ₃ (FT ₃), and elevated free thyroxine (FT ₄)), short stature without GH deficiency, and delayed bone maturation. The entire coding region of the patient's SBP2 was analyzed. GH treatment was initiated when the patient was 4 years old, and combination therapy with GH plus T ₃ was started when the patient was 10 years old.We monitored the patient's height and bone age until he was 11 years old. Results: The patient showed typical symptoms of SBP2 deficiency, and novel compound heterozygous mutations were identified in SBP2 (p.M515fsX563/p.Q79X). Six years of GH monotherapy improved the patient's height S.D. from -3.4 to -1.7 without accelerating bone maturation, whereas 6 months of T ₃ treatment combined with GH almost normalized the thyroid function tests and improved both longitudinal bone growth and maturation. Conclusions: In the growth plate, GH may compensate for decreased local T ₃ effects on longitudinal bone growth; however, GH does not appear to compensate for the effects of T ₃ on bone maturation. We believe that the present case has important implications for understanding the mechanism of thyroid hormone and GH on longitudinal bone growth and maturation.