Generalized arterial calcification of infancy: phenotypic spectrum among three siblings including one case without...

Area of Science:

• Genetics and Molecular Biology
• Pediatric Cardiology
• Rare Diseases

Background:

• Generalized arterial calcification of infancy (GACI) is a rare genetic disorder.
• It is primarily associated with mutations in the ENPP1 gene.
• While often fatal in early infancy, prolonged survival is increasingly observed.

Observation:

• This report details three siblings diagnosed with GACI, exhibiting significant phenotypic variability.
• Two siblings were compound heterozygotes for ENPP1 mutations (c.783C>G and c.878_879delAA).
• Notably, the surviving sibling showed no radiographic calcification or hypophosphatemic rickets.

Findings:

• The study confirms GACI diagnosis in siblings with compound ENPP1 mutations.
• Phenotypic variability includes survival without typical radiographic calcification or rickets.
• This expands the known clinical spectrum of GACI.

Implications:

• GACI may be underdiagnosed, particularly in infants with arterial stenosis but no clear calcification.
• The findings suggest a broader phenotype for GACI than previously recognized.
• The study supports the potential influence of modifying genes on GACI presentation and outcomes.