Table 1.
Clinical and Metabolic Findings in the Two Patients
| Characteristic | Patient 1 This Study: F376V Germline | Patient 2 This Study: F376V Germline | Precocious Puberty and PTH Resistance: A366S Germline | MAS: R201H Postzygotic |
|---|---|---|---|---|
| Serum sodium, mmol/L (normal range: 129–145 mmol/L) | 117–123 | 118–142 | Not reported | Normal |
| Serum PTH, pg/mL (normal range: 15–57 pg/mL) | 66–454 | 90–215 | 570 | Normal |
| Serum alkaline phosphatase, U/L (normal range: 125–380 U/L) | 350–853 | 217–262 | 550–830 | Normal |
| Serum calcium, mmol/L (normal range: 2.2–2.6 mmol/L) | 2.4–2.8 | 2.16–2.4 | 1.4–2.2 | Normal |
| Serum phosphate, mmol/L (normal range: 1.1–2.15 mmol/L) | 1.4–1.8 | 1.75–2.15 | 2.0–3.1 | Normal |
| Serum testosterone (at 3–6 y), ng/mL (normal range: 10–65 ng/mL) | 510–990 | 314–609 | 47–692 | Normal or elevated |
| LH, U/L (30 min after GnRH) | <0.1 | <0.1 | <1 | <0.1 |
| FSH, U/L (30 min after GnRH) | <0.1 | <0.1 | <2 | <0,1 |
| Enlarged testes | + | + | + | +/− |
| Serum free T4, ng/L (normal range: 9.6–17.7 ng/L) or T4, µg/dL (normal range: 5.0–12.0 µg/dL) | 8.4 | 11–13 | 3.1–6.9 (T4) | Normal or high |
| Serum TSH, mU/L (normal range: 0.7–5.9 mU/L) | 0.6–4.1 | 2–2.3 | 1–2.6 | Normal or suppressed |
| Copeptin, pmol/L | ND | 2.4–3.6 | Not reported | Not reported |
| Plasma osmolality, mOsm/kg | 241–271 | 282–290 | Not reported | Not reported |
| Urine osmolality, mOsm/kg | ND | 769–1006 | Not reported | Not reported |
| BMI (SD score) at 3 y | +3.21 | +3.89 | Weight >95th percentile | Normal weight |
| Osteopenia | − | − | + | Not reported |
| Brachydactyly | − | − | + | − |
| Resorptive osteolytic cysts | − | − | + | + |
| Café-au-lait spots | − | (+) | − | + |
Clinical and biochemical findings in the patients with p.F376V in comparison to patients with the combination of pseudohypoparathyroidism and precocious puberty (p.A366S) caused by protein instability (12) or found in MAS (p.R201H) (10). Characteristic findings of the three different diseases are bolded. Parentheses indicate a mild phenotype.
Abbreviations: BMI, body mass index; MAS, McCune-Albright syndrome; ND, not determined; +, present; −, not present; +/−, unilateral testes enlargement.