Figure 17.

Individuals with a mutation in SBP-2 have defects in D2. A, Serum TSH (mU/liter) in affected or unaffected individuals before and during oral administration of incremental doses of l-T₄. Patients with a mutation in SBP-2 required greater doses of T₄ to suppress TSH. B, Serum TSH (mU/liter) and corresponding serum T₃ levels (ng/dl) in affected or unaffected individuals before and during the oral administration of incremental doses of l-T₃ for 5 d. TSH suppression was achieved at similar concentration of serum T₃ in all four subjects. C, D2 enzymatic activity in fibroblasts from two affected children and six unaffected individuals. Baseline (open symbols) and cAMP-stimulated (filled symbols) D2 activity in unaffected (squares) and affected (circles) individuals. The dashed line indicates the limit of detection of the assay. The mean baseline activity in fibroblasts from affected individuals was reduced to near or below the limit of detection and was not inducible by cAMP. D2 mRNA levels were the same in both affected and unaffected individuals (data not shown). [Reprinted with permission from Dumitrescu et al.: Nat Genet 37:1247–1252, 2005 (80).]