Multidisciplinary Clinical Case Study

Hyperphosphatemic Familial Tumoral Calcinosis

Authors: Margaret Kaszycki, MD, Beija Villalpando, MD, LaTonya Hickson, MD, Sarika Rao, MD, Klaas Wierenga, MD, Hillary Garner, MD, Olayemi Sokumbi, MD, Leila Tolaymat, MD

Abstract

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare, autosomal recessive condition characterized by fibroblast growth factor 23 signaling pathway dysregulation, hyperphosphatemia and ectopic calcifications (which manifest as joint motion limitations), inflammatory bony pain, and disability. Given the rarity and multiorgan involvement of HFTC, a multidisciplinary approach including Dermatology, Ophthalmology, Dentistry, Nephrology, Endocrinology, Rheumatology, and Genetics is necessary for diagnosis and treatment. We present a multidisciplinary diagnostic and treatment approach for a patient with HFTC due to a GALNT3 gene mutation with unique imaging highlighting the extent of calcinosis seen in HFTC. In this case study, a 34-year-old female patient found to have HFTC was first evaluated at an outpatient academic dermatology center in October 2020 and studied for 1 year. Genetic testing revealing a homozygous c.1319C > A variant in GALNT3 predicted to result in a missense mutation p.Ala440Glu. HFTC should be considered for patients presenting with diffuse calcinosis cutis-like features, and a multidisciplinary evaluation should be pursued.

 

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References

1. Boyce AM, Lee AE, Roszko KL, et al. Hyperphosphatemic tumoral calcinosis: pathogenesis, clinical Presentation, and challenges in management. Front Endocrinol (Lausanne) 2020;11:293.
 
2. HoBB,Bergwitz C. FGF23 signalling and physiology. JMolEndocrinol2021;66:R23–R32.
 
3. Topaz O, Shurman DL, Bergman R, et al. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet 2004;36:579–581.
 
4. Tiwari V, Zahra F. Last update: August 3, 2023. 'Hyperphosphatemic tumoral calcinosis'. In: StatPearls. Treasure Island (FL): StatPearls. Available at https://www.ncbi.nlm.nih.gov/books/ NBK572152. Accessed May 15, 2024.
 
5. Dayal D, Gupta S, Kumar R, et al. A novel homozygous variant in exon 10 of the GALNT3 gene causing hyperphosphatemic familial tumoral calcinosis in a family from North India. Intractable Rare Dis Res 2021;10:55–57.
 
6. Requena S, Santos-Juanes J, Morales P, et al. Therapeutic success of sodium thiosulfate in treating cutaneous calciphylaxis in a patient with hyperphosphataemic familial tumoral calcinosis. Australas J Dermatol 2022;63:e75–e77.
 
7. Topaz O, Bergman R, Mandel U, et al. Absence of intraepidermal glycosyltransferase ppGalNac-T3 expression in familial tumoral calcinosis. Am J Dermatopathol 2005;27: 211–215.
 
8. Chen S, Francioli, LC, Goodrich, JK, et al. A genomic mutational constraint mapusing variation in 76,156 human genomes. Nature 2024;625:92–100.
 
9. Finer G, Price HE, Shore RM, et al. Hyperphosphatemic familial tumoral calcinosis: response to acetazolamide and postulated mechanisms. Am J Med Genet A 2014;164A:1545–1549.
 
10. Le C, Bedocs PM. Last update: July 10, 2023.'Calcinosiscutis'. In: StatPearls. Treasure Island (FL): StatPearls. Available at https://www.ncbi.nlm.nih.gov/books/NBK448127/. Accessed May 15, 2024.
 
11. Niebel D, Poortinga S, Wenzel J. Osteoma cutis and calcinosis cutis: "similar but different." J Clin Aesthet Dermatol 2020;13:28–31.
 
12. Ichikawa S, Imel EA, Kreiter ML, et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest 2007;117:2684–2691.
 
13. Sanli ME, Kilic A, Aktasoglu E, et al. Familial hyperphosphatemic tumoral calcinosis in an unusual and usual sites and dramatic improvement with the treatment of acetazolamide, sevelamer and topical sodium thiosulfate. J Pediatr Endocrinol Metab 2021;34:813–816.
 
14. Ovejero D, Hartley IR, de Castro Diaz LF, et al. PTH and FGF23 exert interdependent effects on renal phosphate handling: evidence from patients with hypoparathyroidism and hyperphosphatemic familial tumoral calcinosis treated with synthetic human PTH 1-34. JBoneMinerRes2022;37:179–184.
 
15. Dauchez A, Souffir C, Quartier P, et al. Hyperphosphatemic familial tumoral calcinosis with Galnt3 mutation: transient response to anti-interleukin-1 treatments. JBMR Plus 2019;3: e10185.