A Novel Homozygous GALNT3 Deletion in Hyperphosphatemic Familial Tumoral Calcinosis Presenting with Subcutaneous Calcifications and Raynaud's Phenomenon in an Adult Patient: A Case Report.

Abstract

Introduction: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by pathogenic variants in the GALNT3, FGF23, or KL genes, leading to ectopic calcifications. It typically presents in childhood or adolescence with periarticular calcified masses; however, adult-onset cases are exceedingly rare.

Case presentation: We report a 54-year-old woman with a 5-year history of inflammatory bone pain, Raynaud's phenomenon, and distal extremity calcifications. Laboratory evaluation revealed hyperphosphatemia, suppressed parathyroid hormone, elevated 1,25-dihydroxyvitamin D level, and increased tubular phosphate reabsorption, suggesting FGF23 deficiency or resistance. Genetic analysis identified a novel homozygous deletion of exons 8 and 9 in GALNT3. This variant was classified as likely pathogenic per ACMG criteria. The patient was treated with calcium-free phosphate binders, corticosteroids, NSAIDs, and dietary phosphate restriction, resulting in partial symptomatic improvement.

Conclusion: This case represents one of the oldest patients with a genetically confirmed HFTC diagnosis and expands its known phenotypic spectrum. Multidisciplinary evaluation, including genetic counseling and screening of family members, is essential. Awareness of atypical presentations and consideration of genetic testing in patients with unexplained soft-tissue calcifications can facilitate timely diagnosis and management.