From variome to phenome: Pathogenesis, diagnosis and management of ectopic mineralization disorders

Table 4 Differential diagnosis of generalized arterial calcification of infancy[73,78,87-90]

Disease	Distinct differences with GACI
PXE (AR; ABCC6)	GACI-like phenotype possible, however infrequent CV phenotype usually less severe No onset in infancy Dermatological and ophthalmological phenotypes more prominent
Singleton-Merten Calcification (AD; unknown causal gene)	Dental anomalies (delayed eruption and early loss of permanent teeth, alveolar bone erosion) Osteopenia Acroosteolysis
Metastatic calcification due to hypervitaminosis D, hyperparathyroidism or end-stage renal disease	Different distribution of extravascular calcification (renal tubules, bronchial walls and basal mucosa and muscularis mucosae of the stomach) Microscopic vascular changes in media instead of intima
Congenital syphilis	Only calcification of the (ascending) aorta Diagnosed mainly in adults Hutchinson teeth, interstitial keratitis, saber tibiae, saddle-shaped nose Histopathology: endarteritis obliterans of vasa vasorum with perivascular plasma cells, lymphocytic cuffing and adventitial fibrosis
Iliac artery calcification in healthy infants	Only calcification in the common and internal iliac arteries

ABCC6: Adenosine triphosphate-binding cassette, subfamily C, member 6; AD: Autosomal dominant; AR: Autosomal recessive; CV: Cardiovascular; GACI: Generalized arterial calcification of infancy; PXE: Pseudoxanthoma elasticum.