Treatment of Familial Tumoral Calcinosis with Acetazolamide Plus a Phosphate Binder

Introduction:
Familial tumoral calcinosis is an autosomal recessive disease resulting from fibroblast growth factor 23 (FGF23) deficiency or resistance. Subsequent hyperphosphatemia can lead to painful ectopic calcifications, which are often unsuccessfully managed with surgical intervention. We present a case of a patient with intractable pain due to familial tumoral calcinosis who failed surgical management and was given a trial of acetazolamide in addition to calcium acetate.

Case Description:
A 22-year-old female with a history of familial tumoral calcinosis presented for endocrine medical management. In her native country, she developed extensive, painful growths in her left shoulder and hip, for which she underwent surgical tumor debulking. She later developed additional growths in her left elbow and right wrist. Laboratory studies were remarkable for an elevated serum phosphorous level of 7.0 mg/dL (2.5-4.5 mg/dL), parathyroid hormone (PTH) level of 17 pg/mL (15-65 pg/mL), calcium level of 10.1 mg/dL (8.4-10.2 mg/dL) and albumin level of 4.5 g/dL (3.5-5.2 g/dL). FGF23 was found to be markedly elevated at 1,616 RU/mL (44-215 RU/mL). Radiographs of her bilateral shoulders and magnetic resonance imaging (MRI) of her right wrist were consistent with tumoral calcinosis. The patient was reluctant to undergo repeat surgical intervention due to the limited efficacy of her initial procedures. In addition to limiting dietary phosphorous intake, the patient was started on calcium acetate 667 mg three times daily before meals and acetazolamide 250 mg twice daily. Serum phosphorous level subsequently decreased to 6.4 mg/dL. Though she continues to report pain, she has not since developed any new growths.

Discussion:
Familial tumoral calcinosis is a rare disease affecting phosphate metabolism. It is caused by inactivating mutations of the FGF23, klotho or GALNT3 genes, resulting in increased phosphate reabsorption in the kidneys. This excess circulating phosphorous binds to serum calcium, causing deposits to build up in soft tissues that can lead to significant discomfort. Given the high rate of recurrence after surgical intervention, medical management is the mainstay of treatment, focusing on limiting dietary phosphorous intake and absorption. Acetazolamide, a carbonic anhydrase inhibitor, has been proposed as an adjunctive treatment modality. By way of inducing a proximal renal tubular acidosis, acetazolamide can potentially augment the solubility of serum calcium-phosphate complexes, thus promoting renal phosphate clearance. This case serves to highlight both a rare diagnosis and its limited therapeutic options, as well as the potential efficacy of those therapeutic options in patient care.