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

Area of Science:

• Genetics
• Endocrinology
• Rare Diseases

Background:

• Familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare autosomal recessive disorders.
• These conditions stem from mutations in GALNT3, FGF23, or KL genes, leading to hyperphosphatemia and calcification.
• Management includes phosphate-lowering therapies, anti-inflammatories, and surgery for severe cases.

Observation:

• Three cases from a consanguineous family with a homozygous GALNT3 mutation (c.1524+1 G>A) are presented.
• Presentations varied, including chronic osteomyelitis-like symptoms, a gluteal calcified mass, and leg pain.
• These diverse clinical manifestations highlight the varied presentation of the condition.

Findings:

• A specific homozygous mutation in GALNT3 intron eight (c.1524+1 G>A) was identified in all affected family members.
• The study links this genetic mutation to the observed hyperphosphatemia and tumoral calcinosis/hyperostosis.
• Biochemical findings of elevated phosphate levels are crucial indicators.

Implications:

• Recognizing tumoral calcinosis and bony abnormalities alongside elevated phosphate should prompt consideration of HFTC/HHS.
• Family history and biochemical data are vital for diagnosing this rare genetic disorder.
• This case series contributes to understanding the clinical spectrum and genetic basis of GALNT3-related disorders.