Hydrops fetalis as manifestation of generalized arterial calcification of infancy (GACI) (case report)

Introduction: Generalized arterial calcification of infancy (GACI) is a rare autosomal recessive disease caused by mutations in ENPP1. Due to extensive calcification of the arterial tunica media associated with intimal proliferation, the defect leads to vascular occlusions. Most affected children die within the first 6 months of life. To our knowledge only few cases of GACI with hydrops fetalis were reported (1). Case report: We report on a female infant presented with hydrops fetalis. The parents are non-consanguineous of caucasian origin. The pregnancy was uneventful except for unexplainable polyhydramnios. Due to premature rupture of membranes a cesarean section was performed after 32 + 1 weeks of gestation. A hydropic baby with large pericardial effusion was delivered and resuscitation with pericardiocentesis was necessary. No classical causes for generalized hydrops were found. After initial stabilization, she was successfully extubated after 5 days and the remaining hospitalization was remarkable for hip, knee and elbow contractures. Conspicuous echogenic areas in the great arteries' walls of abdominal vessels and the hip joints' capsules were sonographically identified. She was released after 5 weeks of hospitalization. 2½ weeks later, she was readmitted to the NICU with a cardiogenic shock and died after 14 hours despite maximal supportive therapy.- The autopsy revealed generalized arterial and joint calcification and characteristic pathological findings in the vascular tunica elastica interna, compatible with GACI (OMIM #208000). Molecular testing of the ENPP1-gen revealed compound heterozygous mutations: Exon 2: c.286_288delG (p.G96fsX1), paternal origin, and Exon 24: c.2479_2482duplATTC (p.P828HfsX12), maternal origin. Due to the unfavourable prognosis of GACI, a prenatal diagnosis by molecular genetic testing was performed during the following pregnancy with negative result. The mother gave birth to a healthy infant, 1½ year after the baby of the reported case passed away. Conclusion: GACI might be one of the possible etiologies of hydrops fetalis. The typical sonographic findings of echogenic areas in the great arteries' walls and the joints' capsules can lead to early diagnosis.

(1) Idiopathic infantile arterial calcification: The spectrum of clinical presentations. Chong C, Hutchins G. Pediatr Dev Pathol (Aug 2007: 1)