Two newborn babies with generalized arterial calcification of infancy, two new mutations

Yapıcıoğlu-Yıldızdaş, Hacer; Özbarlas, Nazan; Erdem, Sevcan; Yılmaz, Mehmet; Özlü, Ferda; Büyükkurt, Selim; Soyupak, Süreyya; Gullu, Utku Ufuk; Karaer, Kadri

doi:10.24953/turkjped.2016.04.013

Cited by 5 publications

(6 citation statements)

References 16 publications

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“…However, analogs of PP i , the bisphosphonates, are already in clinical use for the treatment of osteoporosis, despite the rare but severe adverse effects (e.g., jaw necrosis). Moreover, bisphosphonates have been shown to reduce ectopic calcification in patients with GACI (99, 100) or PXE (101), and in animal models of PXE and CKD (17, 97, 102).…”

Section: Endogenous Vascular Calcification Inhibitor As Therapeutic Amentioning

confidence: 99%

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Bäck

Arányi

Cancela

et al. 2019

Front. Cardiovasc. Med.

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The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PPi). The importance of PPi for inhibiting arterial calcification has been reinforced by the protective effects of PPi in various mouse models displaying ectopic calcifications. Besides PPi, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or Mgp-deficient mice develop spontaneous calcification of the arterial media. Whereas PPi and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification.

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Section: Endogenous Vascular Calcification Inhibitor As Therapeutic Amentioning

confidence: 99%

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Bäck

Arányi

Cancela

et al. 2019

Front. Cardiovasc. Med.

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“…Generalized arterial calcification of infancy is a rare autosomal recessive disorder characterized by congenital calcification of large and medium sized arteries. The calcification of arterial structures is initiated in the internal elastic lamina and extends into the intima and media, being accompanied by fibrous thickening of the intima, which causes luminal narrowing ( 17 ). There are two forms of GACI.…”

Section: Discussionmentioning

confidence: 99%

Severe early-onset manifestations of generalized arterial calcification of infancy (mimicking severe coarctation of the aorta) with ABCC6 gene variant — Case report and literature review

Făgărășan

Gozar

Ghiragosian

et al. 2022

Front. Cardiovasc. Med.

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IntroductionGeneralized arterial calcification of infancy (GACI) is a rare cause of infantile heart failure and systemic hypertension with a poor prognosis, characterized by extensive calcification and proliferation of the intimal layer of large and medium sized arteries.Case reportWe present the first case report of successful surgical treatment of severe aortic arch obstruction by calcified plaques mimicking severe coarctation of the aorta and the outcome (of bisphosphonate therapy) in a newborn with GACI. Furthermore, we report the identification of a variant in ATP Binding Cassette Subfamily C, Member 6 (ABCC6) gene, possibly associated with severe early-onset manifestations of GACI.ConclusionThis case report highlights the importance of considering GACI in an infant with heart failure, systemic hypertension, and evidence of increased echogenicity of the arterial vessels. We noted the favorable outcome in improving the aortic calcification in our patient after surgical treatment and bisphosphonates therapy. Early diagnosis and treatment improve the long-term prognosis. A better understanding of this rare genetic disease could lead to new therapeutic strategies.

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“…GACI is defined by marked calcification of the internal elastic membrane of the large and medium-sized arteries, fibroblastic proliferation in the intima, and a giant cell reaction ( 3 , 6 , 11 ). Coronary arteries were mostly described to be narrowed, with ventricular dysfunction or myocardial infarction as the major complications ( 7 , 11 , 16 , 17 ). In our case, no signs of myocardial ischemia, myocarditis, nor foci of calcification were seen in the coronaries.…”

Section: Discussionmentioning

confidence: 99%

“…It is a rare fatal disease that presents in early infancy ( 2 ). With 50 cases reported before 1971 ( 3 ) and another 150 reported worldwide since then ( 4 – 7 ), it occurs with an estimated frequency of 1:390,000 infants ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Coexistence of generalized arterial calcification of infancy (GACI) and maternal infections with cytomegalovirus and Toxoplasma gondii-unexpected fatal complication in a newborn

et al. 2022

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Generalized arterial calcification of infancy (GACI) is an extremely rare autosomal recessive condition characterized by the storage of calcium at the level of internal elastic membrane of arteries. The main consequences are intimal fibrous thickening and arterial occlusion. We present the case of a preterm male infant, born from an improperly dispensed pregnancy. At birth, the newborn presented generalized edema and hypotonia, and abolished heart sounds, without response to stimulation. Despite the mechanical ventilation, the infant died 2 h after birth. The death was clinically presumed to be related to the maternal infection with cytomegalovirus (CMV) and Toxoplasma gondii. The infant's mother affirmed the history of 6 previous miscarriages and a non-consanguineous marriage. At autopsy, microscopic examination showed generalized vasculitis secondary to minimal calcification of the large and medium-sized vessels of the lungs, liver, and tongue. These findings supported the diagnosis of GACI. Hydrothorax, non-infective ascites, and necrosis of the brain parenchyma were also associated. The premature infant died due to tonsillar herniation associated with decreased vessel compliance and refractory pulmonary hypertension thus leading to congestive cardiac failure. CMV was not detected on histopathological assessment nor were signs of any other infections. To the best of our knowledge, this is the first case of GACI occurring in a baby from a mother co-infected with CMV and T. gondii.

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Two newborn babies with generalized arterial calcification of infancy, two new mutations

Cited by 5 publications

References 16 publications

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Severe early-onset manifestations of generalized arterial calcification of infancy (mimicking severe coarctation of the aorta) with ABCC6 gene variant — Case report and literature review

Case Report: Coexistence of generalized arterial calcification of infancy (GACI) and maternal infections with cytomegalovirus and Toxoplasma gondii-unexpected fatal complication in a newborn

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