Bone Abstracts

Background: Mutations in the ENPP1 gene have been identified in individuals with generalized arterial calcification of infancy (GACI), a life-threatening disorder characterized by calcification in the blood vessels, because of reduced availability of pyrophosphate. We describe a case of GACI due to a novel ENPP1 mutation.

Presenting problem: The patient, born at term to non-consanguineous parents, was referred to us at birth with weak femoral pulses for exclusion of aortic coarctation. Echocardiography showed left ventricular hypertrophy and low contractility, but normal aortic arch dimensions. Doppler studies revealed increased echogenicity of the wall of various arteries (common hepatic and splenic arteries, renal, iliac, femoral, carotid arteries and abdominal aorta), which within a 2-week interval progressed to frank calcifications. His cranial ultrasound revealed calcifications of the anterior cerebral and right lenticulostriate artery, as well as dilatation of the 3rd and 4th ventricle. His growth was within normal limits and he had no dysmorphic features.

Clinical management: Upon Doppler imaging and clinical n suspicion of GACI he was started on IV infusions of pamidronate (0.1 mg/kg/week for 4 weeks), followed by oral risedronate (1 mg/kg/week), with close monitoring of growth, bone metabolism and progress of his calcification. Sequence analysis of ENPP1 gene was performed; the patient was found homozygote for the novel ENPP1 mutation c.825C>G in exon 8, which results in the substitution of an isoleucine by a methionine (ENPP1: p.Ile275Met). Both parents were heterozygous for the same mutation. The patient developed resistant hypertension requiring three antihypertensive medications. He also had a V-P shunt inserted and adequate calcium and vitamin D supplementation. He is now two years old and still on the aforementioned treatment. His calcifications have nearly regressed and his growth and neurodevelopment are satisfactory. However, his hypertension is still very hard to control and left ventricular hypertrophy remains unchanged.

Discussion: We identified a novel ENPP1 mutation causing GACI in our index patient. To our knowledge, this is the first time that hydrocephalus and calcifications of cerebral arteries are described in this disorder. More importantly, unexplained, drug-resistant hypertension requires a comprehensive Doppler study of all arteries to exclude rarities like this.

Disclosure: The authors declared no competing interests.