Perinatal Diagnosis of Generalized Arterial Calcification of Infancy: First Genetically Confirmed ENPP1 Case in an...

Generalized Arterial Calcification of Infancy (GACI) is a rare genetic vascular disease characterized by the early onset (between in utero and infancy) of extensive calcification and stenosis of the large and medium-sized arteries. Presentation is typically with respiratory distress, congestive heart failure, and systemic hypertension. With approximately 300 cases reported worldwide in the medical literature. The prevalence is unknown; however, based on the carrier frequency of the recognized pathogenic variants, a frequency of 1 in 200,000 has been suggested. The autosomal recessive form of GACI disorder is caused by mutations in the ENPP1 or ABCC6 genes. To the best of our knowledge, this study represents the first genetically confirmed case of GACI in an Egyptian fetus detected during the perinatal period. In this report, we describe a case of GACI in a fetus with a pathogenic ENPP1 gene mutation at 29 weeks of gestation. Ultrasound examination revealed aortic and pulmonary valve stenosis, biventricular hypertrophy, and a hypercalcified aorta and ductal arch. Genetic testing identified a homozygous pathogenic variant in the ENPP1 gene: c.749C>T (p.Pro250Leu). In conclusion, early diagnosis of GACI is vital due to its severe prognosis and early symptom onset. Expert fetal echocardiography plays a key role in detecting arterial calcification during pregnancy. Genetic testing enhances diagnostic accuracy, informs treatment strategies, and supports family counselling.