# Three Siblings With a Rare Familial Hyperphosphatemia Syndrome: A Case Series

## TL;DR

This paper reports three siblings with a rare inherited condition causing high phosphate levels and bone and tissue abnormalities due to a specific genetic mutation.

## Contribution

The study identifies a novel homozygous mutation in the GALNT3 gene in a consanguineous family with familial hyperphosphatemia syndrome.

## Key findings

- Three siblings from a consanguineous family shared a homozygous GALNT3 mutation (c.1524+1 G>A).
- The condition presented with varied symptoms including calcified masses and bone pain.
- Diagnosis relied on clinical findings, family history, and elevated phosphate levels.

## Abstract

Hyperphosphatemia familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare autosomal recessive disorders caused by mutations in the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), fibroblast growth factor 23 (FGF23), or klotho (KL) genes. They are characterized by hyperphosphatemia and recurrent episodes of bone lesions with hyperostosis and/or soft tissue calcinosis. Management options include phosphate-lowering therapies, anti-inflammatory medications, and surgical excision of the calcified masses in significantly disabled cases. We describe three cases from a consanguineous family who were found to have the same genetic mutation caused by a homozygous mutation in intron eight of GALNT3 c.1524+1 G>A (IVS8+1). The first case had a presentation similar to chronic osteomyelitis, while the second one presented with a calcified mass in her gluteal area. The third case presented with left leg pain. Being a rare disease, the findings of tumoral calcinosis/ bony abnormalities, along with elevated phosphate levels, should raise the possibility of this entity. Family history and biochemical findings can help reach the diagnosis.