Hyperphosphatemic familial tumoral calcinosis: Response to acetazolamide and postulated mechanisms

Gal Finer, Heather E. Price, Richard M. Shore, Kenneth E. White, Craig B. Langman

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by enhanced renal phosphate absorption, hyperphosphatemia, and tumor-like extraosseous calcifications due to inactivating mutations in FGF23 or associated proteins. Surgical excision is needed when low phosphate diet and phosphate binders are ineffective. Sporadic reports have supported acetazolamide use. We report on a 7-year-old African American boy who presented with severe HFTC requiring numerous surgical excisions. Tumors continued to appear and others reoccurred despite phosphate restriction and sevelamer carbonate. At the age of 9.5 years, acetazolamide (40mg/kg/day) was added and resulted in mild metabolic acidosis (bicarbonate 25.3mEq/L vs. 21.4mEq/L, P<0.001; serum pH 7.38 vs. 7.31, P=0.013, pre- and post-acetazolamide, respectively) but no change in tubular reabsorption of phosphate (TRP) (96.9% vs. 95.9%, P=0.34) or serum phosphate (6.6mg/dl vs. 6.9mg/dl, P=0.52 pre- and post-acetazolamide, respectively). Following the initiation of acetazolamide therapy, the patient experienced significant improvement in disease course as indicated by resolution of localized bone pain, cessation of tumor formation, and no tumor recurrence. Despite mild metabolic acidosis, our patient had improved linear growth and did not develop any other side effects related to therapy. Intact FGF23 remained abnormally low throughout disease course, while C-terminal FGF23 increased with acetazolamide. We conclude that acetazolamide can control severe HFTC by inducing mild metabolic acidosis despite no change in serum phosphate or TRP. This effect may be exerted though improved calcium-phosphate complex solubility and increased FGF23 locally.

Original languageEnglish
Pages (from-to)1545-1549
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number6
StatePublished - 1 Jan 2014
Externally publishedYes


  • Acetazolamide
  • Calcifications
  • Calcium-phosphate solubility
  • FGF23
  • GALNT3
  • Hyperphosphatemia
  • Hyperphosphatemic familial tumoral calcinosis
  • Metabolic acidosis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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