Search

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values—SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1 cm3, n = 9) and lesion volume (282.5 ± 414.8 cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden. Lay Summary: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder in which patients develop sometimes large debilitating calcifications of soft tissues and blood vessels. It is caused by deficient fibroblast growth factor-23 that leads to high phosphate levels, which contributes to the calcifications. The calcifications and manifestations of this disorder have not been well characterized. We determined the mineral composition of the calcifications to be hydroxyapatite. Capitalizing on the fact fluoride can be integrated into hydroxyapatite, we used radiolabeled sodium fluoride PET/CT scans (18F-NaF PET/CT) to characterize and quantify the calcifications in 11 patients. Eighty-two percent of the patients had calcifications, with the largest located at the hips and shoulders. Micro-calcifications were found in the blood vessels of most patients, including children. The technique also enabled us to differentiate between active vs stable calcifications. This first systematic assessment of calcifications in patients with HFTC showed the utility of 18F-NaF PET/CT as a tool to identify and quantify calcifications, as well as distinguish between active and stable calcifications. This approach will inform disease progression and may prove useful for measuring response to treatment. Graphical Abstract [ABSTRACT FROM AUTHOR]

AimHyperphosphatemic Familial Tumoral Calcinosis (HFTC) is an autosomal recessive disorder. This study investigates the etiology of HFTC in offspring from consanguineous parents. Methods: Clinical assessment, imaging, and direct sequencing were utilized to elucidate the condition. Previously reported cases were also reviewed. Result: We identified a consanguineous Chinese family with HFTC caused by an interesting homozygous G to A substitution in GALNT3 (c.1626 + 1G > A). The parents were carriers. Conclusion: This study represents the first report of HFTC in a consanguineous Chinese family due to an interesting GALNT3 mutation. We reviewed known GALNT3 variants and associated clinical features of calcification disorders. The phenotypic difference between homozygous and complex heterozygous mutations is not clinically significant. Gene mutations affect the function of proteins mainly by affecting their binding to polyvalent ligands.

Aim Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is an autosomal recessive disorder. This study investigates the etiology of HFTC in offspring from consanguineous parents., Methods: Clinical assessment, imaging, and direct sequencing were utilized to elucidate the condition. Previously reported cases were also reviewed., Result: We identified a consanguineous Chinese family with HFTC caused by an interesting homozygous G to A substitution in GALNT3 (c.1626 + 1G > A). The parents were carriers., Conclusion: This study represents the first report of HFTC in a consanguineous Chinese family due to an interesting GALNT3 mutation. We reviewed known GALNT3 variants and associated clinical features of calcification disorders. The phenotypic difference between homozygous and complex heterozygous mutations is not clinically significant. Gene mutations affect the function of proteins mainly by affecting their binding to polyvalent ligands., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Published by Elsevier Inc.)