Table 1.
Demographic, Dental, Clinical, Biochemical, and Genetic Findings in Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) Cohort at Initial Visit
| Patient | Age at symptom onset/current age (y) | Length of follow‐up (y) | Gender | Dental calcification a | Vascular calcification | Soft tissue calcification b | Phosphate c (age‐specific normal range mg/dl) | FGF23 | Genetic mutation e | Treatment | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intact (22–63 pg/ml) | C‐term d (≤230 RU/ml) | Gene | DNA change | |||||||||
| 1 | 12/48 | 12 | F | Y | N | 1+ | ↑ 7.3 (2.5–4.8) | ↓ 17 | ↑ 1210 | GALNT3 | c.1312C>T, c.1774C>T | ACZ, NC |
| 2 f | 5/17 | 11 | F | Y | Y | 2+ | ↑ 8.8 (3.1–5.5) | 34 | ↑ 2880 | GALNT3 | c.516‐2A>T, c.260_266del | SEV, ACZ, PB, AL, CAN |
| 3 f | 9/15 | 7 | F | Y | N | 0 | ↑ 6.8 (3.1–5.5) | 39 | ↑ 1985 | GALNT3 | c.516‐2A>T, c.260_266del | SEV, ACZ, PB |
| 4 g | 10/38 | 9 | M | Y | Y | 3+ | ↑ 5.5 (2.5–4.8) | ↓ 8 j | ↑ 660 | GALNT3 | c.1584dup | SEV, ACZ, PB, NC, AL, TT, ANA, CAN |
| 5 g | None/25 | 6 | M | Y | N | 0 | ↑ 5.5 (2.5–4.5) | 39 | ↑ 971 | GALNT3 | c.1584dup | n/a |
| 6 | 3/20 | 8 | F | Y | N | 1+ | ↑ 6.6 (3.1–5.5) | 38 j | ↑ 884 | GALNT3 | c.516‐2A>T, c.1524+5G>A | SEV, ACZ, PB |
| 7 | 45/63 | 6 | F | N | Y | 3+ | 4.8 (2.5–4.8) | 46 j | ↑ 1190 | Unknown | n/a | SEV, ACZ, PB |
| 8 | 1/12 | 5 | F | n/a | N | 2+ | ↑ 7.0 (3.0–5.7) | 22 | ↑ 1031 | GALNT3 | c.746_749del, c.892del | SEV, ACZ, PB |
| 9 | 6 mo/19 | 6 | F | n/a i | N | 2+ | ↑ 5.3 (2.5–5.1) | 42 | 66 | KLOTHO | arr 13q13.1q14.3(32,887,503‐53,157,340)x4 dn k | n/a |
| 10 | 3 wk/12 | 5 | M | Y | N | 2+ | ↑ 7.2 (3.2–6.3) | ↑ 13,000 | ↑ 33,000 | Autoimmune | n/a | SEV, ACZ, PB, TT |
| 11 | 10/47 | 4 | M | Y | Y | 3+ | ↑ 5.4 (2.5–4.5) | ↓ 19 | ↑ 1420 | GALNT3 | c.766G>C k | SEV, ACZ, PB |
| 12 | 11/46 | 3 | M | Y | Y | 2+ | ↑ 6.5 (2.5–4.5) | 41 | ↑ 890 | FGF23 | c.211A>G, c.107G>A k | SEV, ACZ |
| 13 g | 8/27 | 2 | F | Y | N | 2+ | ↑ 6.4 (2.5–4.5) | ↓ 21 | ↑ 1470 | GALNT3 | c.1584dup | n/a |
| 14 f | None/2 | 1 | M | n/a | N | 0 | ↑ 7.4 (3.1–6.0) | 23 | ↑ 2260 | GALNT3 | c.516‐2A>T, c.260_266del | SEV |
| 15 | 7/53 | 1 | F | Y | Y | 3+ | ↑ 5.8 (2.5–4.5) | ↓ 16 | ↑ 1910 | Unknown | n/a | LC, ACZ, ANA, SEV |
| 16 | 4/12 | 1 | F | Y | N | 2+ | ↑ 7.1 (3.0–5.7) | 23 | ↑ 1860 | GALNT3 | c.985G>A k , c.1677_1680dup k | SEV, ACZ, AL, TT |
| 17 | 10/74 | 1 | F | Y | Y | 2+ | ↑ 5.4 (2.5–4.5) | 31 | ↑ 2450 | GALNT3 | c.746_749del, c.926T>G k | SEV |
| Range h | 1–45/2–74 | 1–12 | Prevalence h | 4.8–8.8 | 8–46 | 660–2880 | ||||||
| Mean h | 10.4/33.3 | 5.1 | 5 M 10 F | 12/13 | 7/15 | 12/15 | 6.4 | 27.8 | 1538.1 | |||
| Median h | 9/27 | 5 | 6.5 | 23 | 1420 | |||||||
Abbreviations: ACZ, acetazolamide; AL, aluminum hydroxide; ANA, anakinra; CAN, canakinumab; FGF23, fibroblast growth factor 23; GALNT3, UDP‐GalNAc:polypeptide N‐acetylgalactosaminyltransferase 3; HFTC, hyperphosphatemic familial tumoral calcinosis; LC, lanthanum carbonate; n/a, not available; NC, nicotinamide; PB, probenecid; SEV, sevelamer; TT, topical thiosulfate.
More detailed dental data provided in Supplementary Information Table S3.
Soft tissue calcification grading: 0 normal – 3+ severe.
To convert phosphate to mmol/L, multiply by 0.323.
C‐terminal FGF23 [3M–17Y ≤230, ≥18 Y ≤ 180 RU/mL].
More genetic data included in Supplementary Information Table S2.
Patients 2, 3, and 14 are siblings.
Patients 4, 5, and 13 are siblings.
Calculated excluding patients 9 and 10.
Dental radiographs were not available. An exfoliated primary tooth had normal pulp morphology, but increased pulp density (200.8 mg HA/cm3) by μCT analysis.
Some iFGF23 were measured by Kainos Laboratories. The rest were measured by Immutopics Quidel.
Novel mutation.