Generalized arterial calcification of infancy (GACI) is a rare autosomal recessive disease caused by mutations in ENPP1. Due to extensive calcification of the arterial media associated with intimal proliferation leading to vascular occlusion, most affected children die within the first 6 months of life. We report on two Taiwanese siblings with an identical genotype, but different clinical course. The male sibling developed heart failure and severe hypertension, and died at the age of 6 weeks despite of treatment with bisphosphonates, ACE inhibitors, and hydralazine. The subsequent female, who was monitored closely pre- and post-natally, is having an uncomplicated clinical course up to the age of 1(1/2) year now. There were similar characteristic sonographic and roentgenographic findings in both siblings in early infancy. In both siblings, the same compound heterozygous mutations (c.1025G > T [p.Gly342Val] and c.1112A > T [Tyr371Phe]) in ENPP1 were identified. Despite the same genotype and similar sonographic and radiographic features in early infancy, the phenotype of GACI can vary to a great extent within one family.
Copyright 2005 Wiley-Liss, Inc.