Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management

AbstractPurpose of ReviewThis review summarizes current understanding of generalized arterial calcification of infancy (GACI), emphasizing pathophysiology, clinical presentation, and approaches and controversies in management.Recent FindingsIdentification of causativeENPP1 mutations revealed that GACI arises from deficiencies in inorganic pyrophosphate (leading to calcifications) and adenosine monophosphate (leading to intimal proliferation). Identification of genotypic and phenotypic overlap with pseudoxanthoma elasticum and autosomal recessive hypophosphatemic rickets further advanced understanding of GACI as a complex, multisystemic disease. Clinical data is limited to small, retrospective samples; it is therefore unknown whether commonly used medications, such as bisphosphonates and hypophosphatemia treatment, are therapeutic or potentially harmful. ENPP1-Fc replacement represents a promising approach warranting further study.SummaryKnowledge gaps in natural history place clinicians at high risk of assigning causality to interventions that are correlated with changes in clinical status. There is thus a critical need for improved natural history studies to develop and test targeted therapies.
Source: Current Osteoporosis Reports - Category: Orthopaedics Source Type: research