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Generalized arterial calcification of infancy (GACI) is a rare condition characterized by diffuse arterial calcification within the internal elastic lamina associated with intimal proliferation leading to stenosis of great and medium-sized vessels, which causes end-organ damage and loss of life during infancy. The clinical presentation of acute renal failure with normal cardiac function is rare. A 7-day-old female neonate was admitted with a clinical impression of late-onset neonatal sepsis, meningitis, and acute kidney injury after developing a high-grade fever, abnormal body movements, and vomiting of the ingested matter associated with decreased urinary output. On laboratory tests, she had abnormal urea and creatinine levels, multiple electrolyte abnormalities, and a negative septic workup. Ultrasonography revealed diffuse arterial calcification that also involved the renal arteries and renal parenchyma bilaterally. She was clinically diagnosed with GACI and initiated on supportive care including renal replacement therapy. However, she died at the age of 42 days. This case highlights that GACI can present as unexplained acute kidney injury associated with generalized arterial calcification. Ultrasound can be optimized to aid in diagnosis in resource-limited settings.

Generalized arterial calcification of infancy (GACI) is a rare autosomal-recessive disease characterized by extensive arterial calcification in infancy, with clinical manifestations such as arterial stenoses and heart failure. The ENPP1 inactivation mutation has been identified as a potential defect in most of the cases of GACI, while mutations in ABCC6 are demonstrated in patients who are genotyped as pseudoxanthoma elasticum and only limited cases of GACI are reported. Whole-exome sequencing was applied for the detection of pathogenic variants. Copy-number variants of pathogenic genes were also evaluated through a bioinformatic process and were further validated by real-time quantitative PCR. In this report, we described the clinical information and treatment of a patient with extensive arterial calcification. We have identified the underlying cause as biallelic mutations in ABCC6 (NM_00117: exon30, c.4223_4227dupAGCTC p.(Leu1410Serfs*56)) and a unique exonic deletion that spans from the first to the fourth exons of ABCC6 (chr16:16313388-16330869)). This discovery was made by utilizing a combined genetic testing approach. With the review of previously reported GACI patients with ABCC6 mutation, our work contributed to enriching the mutation spectrum of GACI and providing further information on this rare form of inherited disorder. [ABSTRACT FROM AUTHOR]

Generalized arterial calcification of infancy (GACI) is a rare autosomal-recessive disorder, characterized by calcification of the internal elastic lamina, fibrotic myointimal proliferation of muscular arteries and resultant arterial stenosis. Treatment with bisphosphonates has been proposed as a means of reducing arterial calcifications in GACI patients, although there is no formalized treatment approach. The case reported here was a patient with severe GACI diagnosed at three months of age who had no response to bisphosphonate treatment, but clinically improved after the initiation of magnesium and anti-phosphate (using calcium carbonate) treatments. In patients unresponsive to bisphosphonate, magnesium and anti-phosphate treatment may be attempted.

Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal‐recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54‐year‐old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima‐media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C‐terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Generalized arterial calcification of infancy (GACI) is a rare autosomal-recessive disorder, characterized by calcification of the internal elastic lamina, fibrotic myointimal proliferation of muscular arteries and resultant arterial stenosis. Treatment with bisphosphonates has been proposed as a means of reducing arterial calcifications in GACI patients, although there is no formalized treatment approach. The case reported here was a patient with severe GACI diagnosed at three months of age who had no response to bisphosphonate treatment, but clinically improved after the initiation of magnesium and anti-phosphate (using calcium carbonate) treatments. In patients unresponsive to bisphosphonate, magnesium and anti-phosphate treatment may be attempted. [ABSTRACT FROM AUTHOR]

Background A baby girl developed respiratory distress immediately after birth and required supplemental oxygen. She was born at term via lower-segment cesarean section. The parents Wire nonconsanguineous, and antenatal ultrasonography during the pregnancy at 18 and 32 weeks of gestation did not reveal any abnormalities. On examination at birth, no pulses were palpable; however, the baby's blood pressure was normal and no remarkable abnormalities were detected. Ultrasonography revealed widespread arterial calcification. Investigations Chest and abdominal radiography at birth and serial abdominal, renal and cardiac ultrasonography at follow-up examinations; dual-energy X-ray absorptiometry during treatment with bisphosphonates; genetic screening. Diagnosis Generalized arterial calcification of infancy, secondary to compound, heterozygous mutations the ENPP1 gene, pL661V and pE668K of the paternal chromosome, and pN792S the maternal chromosome. Management Low-dose disodium pamidronate (0.1 mg/kg per week for 4 weeks), which commenced on the seventh day after birth and was changed to oral risedronate sodium (1 mg/kg per week as a single dose) at 4 weeks of age. Complete resolution of arterial calcification was seen by 3 months of age. At 12 months, ergocalciferol was added at a dose of 5,000 U daily for 6 weeks, followed by 200 U daily owing to the patient's vitamin D deficiency and elevated parathyroid hormone level. Treatment with bisphosphonates is ongoing, but is planned to be discontinued at 3 years of age. The child has remained healthy and developmentally normal. [ABSTRACT FROM AUTHOR]