Hyperphosphatemic Familial Tumoral Calcinosis with Hyperphosphatemic Hyperostosis Due to a Novel Mutation: Severe Presentation of a Rare Disorder

Abstract

Tumoral calcinosisis (TC) is a rare disorder characterized by abnormal deposition of calcium in subcutaneous tissues. It can be primary or secondary to systemic diseases. The primary familial form with hyperphosphatemia has been described to be due to underlying biallelic variants in GALNT3, KLOTHO, or FGF23 gene which lead to the inactivation of FGF23 resulting in hyperphosphatemia and its effects thereof. These patients usually present only with TC or diaphysitis with cortical hyperostosis, known as hyperphosphatemic-hyperostosis syndrome (HHS), and rarely present with both. We present a 13-year-old boy with a history of painful swelling of the right hip joint for the last 4 years who was found to have hyperphosphatemic familial TC on evaluation with HHS of the left tibia due to an underlying novel homozygous missense variant in GALNT3 gene. Further, in silico analysis was carried out to identify the impact of this missense variant on the structure and function of protein coded by GALNT3.