Table 1.
Summary of Clinical, Biochemical, and Treatment Profiles of Patients With Dominant-Negative Mutations in the GHR
| P1 | P2 | P3 | P4 | |||
|---|---|---|---|---|---|---|
|
| ||||||
| c.964dupG/WT | c.920_921ins14/WT | c.945+2T>C/WT | c.899dupC/p.R229H | |||
| Mutation | Duplication | Insertion | Splicing | Duplication | ||
| Age, y | 3.4 | 3.8 | 12 | 4.2 | ||
| Sex | Female | Male | Female | Male | ||
| Height, cm (SD) | 84 (−3.09) | 88.8 (−3.1) | 119.6 (−4.3) | 85.4 (−4.17) | ||
| Weight, kg (SD) | 11.3 (−2.36) | 11.3 (−2.0) | NA | 11.4 (−3.66) | ||
| Ethnicity | Northern European/Hispanic | Spanish | Spanish | Pakistan | ||
| Birth week | 39 | 37 | NA | NA | ||
| Birth weight, kg (SD) | 3.56 (+0.23) | 2.6 (−0.7) | NA | 3.38 | ||
| Birth length, cm (SD) | 49.5 (−0.29) | 48 (−0.3) | NA | 48 | ||
| Paternal height, cm (SD) | 161.5 (−2.1) | 164 (−1.8) | 150.5 (−3.6) | 180.3 (+0.48) | ||
| Maternal height, cm (SD) | 157 (−0.98) | 149.5 (−2.46) | 138.6 (−4.3) | 154.4 (−1.38) | ||
| Biochemistry | ||||||
| GH basal, ng/mL | 4.3 | NA | 56.6 | 8 | ||
| GH stimulated | 14.1 ng/mL (clonidine) | 17.7 mU/L (clonidine) | NA | 37 ng/mL (arginine) | ||
| IGF-I, ng/mL (RR) | <25 (49–290) | 69 (55–297) | 43 (126–1188) | 16 (54–178) | ||
| IGFBP-3, mg/L (RR) | 1.1 (0.9–4.5) | NA | 0.87 (2.0–9.3) | 0.7 (0.8–3.0) | ||
| ALS, mg/L (RR) | 4.6 (2.3–11) | NA | 7.4 (14–29) | 2.6 (1.9–10) | ||
| GHBP, pmol/L (RR) | 1991 (267–1638) | NA | 35,634 (534–5785) | 1379 (267–1638) | ||
| Treatment | ||||||
| Treatment | rhIGF-I | rhGH | rhGH + rhIGF-I | rhIGF-I + rhIGFBP-3 | rhIGF-I | rhGH + rhIGF-I |
| Dose | 120 μg/kg bid | 0.035 mg/kg/d | 0.035 mg/kg/d (rhGH) + 40 μg/kg/d (rhIGF-I) | 1 mg/kg/da | 120 μg/kg bid | 0.04 mg/kg/d (rhGH) + 90 μg/kg bid (rhIGF-I) |
| Age, y | 8.8 | 12.08 | 14.8b | 15 | 4.7 | 11.7b |
| IGF-1, ng/mL (RR) | 206 (57–305) | 87 (80–690) | 309 (180–820) | NA | 211 (36–202) | 326 (86–393) |
| IGFBP3, mg/L (RR) | NA | 3.4 (2.1–9.2) | 3.73 (>3.1) | NA | 0.6 (1–4.7) | 0.9 (2–4.8) |
| ALS, mg/L (RR) | NA | NA | NA | NA | NA | 3.3 (5.6–6) |
| Reference | This study | This study | This study | Aisenberg et al. (2010) Derr et al. (2011), this study |
||
Abbreviations: bid, twice daily; NA, not available; RR, reference range.
a
rhIGF-I + rhIGFBP3 combination therapy that is no longer available.
b
Tanner II–III, testes 8 mL.