Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome

Area of Science:

• Pediatric Endocrinology
• Rare Diseases
• Biochemistry

Background:

• Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease.
• Children with HGPS exhibit extraskeletal calcifications, impacting their health.
• Understanding the development of these calcifications is crucial for patient management.

Purpose of the Study:

• To describe the natural history and pathophysiology of extraskeletal calcifications in HGPS.
• To determine if medications and supplements alter calcification development in HGPS patients.

Main Methods:

• Children in two clinical trials (lonafarnib, lonafarnib+pravastatin+zoledronic acid) were assessed at baseline, one year, and end-of-therapy.
• Calcifications were evaluated via physical exams, radiographs, and biochemical measures.
• Mineral content of calcifications was analyzed using x-ray diffraction.

Main Results:

• Extraskeletal calcifications were present in 31% of patients at baseline and increased with age.
• Calcium carbonate supplementation significantly increased calcification odds, which plateaued after discontinuation.
• Hydroxyapatite was identified as the composition of calcifications; plasma magnesium decreased, and PTH increased with lonafarnib therapy.

Conclusions:

• Extraskeletal calcifications in HGPS increase with age and are composed of hydroxyapatite.
• The mechanism may involve decreased plasma magnesium and FGF23, with PTH increasing after lonafarnib.
• Calcium carbonate is not recommended for routine supplementation in children with HGPS due to accelerated calcification.