Presentation
The clinical presentation was characterized by a severe early-onset of hypertension refractory to multiple therapy. [ncbi.nlm.nih.gov]
Early-onset disease presents variably with fetal distress, heart failure, polyhydramnios, hypertension, respiratory distress, hydrops fetalis, edema, visceral effusions, cyanosis, cardiomegaly, and ascites. [orpha.net]
Entire Body System
-
Plethora
Chest radiography showed cardiomegaly and pulmonary plethora. Electrocardiography showed left ventricular hypertrophy and strain pattern. [doi.org]
[…] ventricles Extramedullary hematopoiesis of liver Hypertrophy of myocardium Bright and hyper-reflective myocardium Periarticular calcifications in the wrists, ears, shoulders, ankles and hip Heart usually looks structurally normal Cardiomegaly and pulmonary plethora [en.wikipedia.org]
-
Large Pericardial Effusion
The fetal and postnatal echocardiographic features were a large pericardial effusion, thickened pulmonary and aortic valves, poor pulsation of the descending aorta, and calcification of the great vessels. [doi.org]
A hydropic baby with large pericardial effusion was delivered and resuscitation with pericardiocentesis was necessary. No classical causes for generalized hydrops were found. [thieme-connect.com]
-
Wheelchair Bound
He was receiving EHDP, 200 mg/day orally, and had odynodysphagia, diffuse opioid-controlled pain, plagiocephaly, facial dysmorphism, joint calcifications, contractures, and was wheelchair bound. [ncbi.nlm.nih.gov]
Skin
-
Skin Edema
The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. [ncbi.nlm.nih.gov]
Workup
The infant died at the age of 7 weeks of cardiac failure and the parents were referred to Molecular Biology and Cytogenetic lab for further workup. [jcdronline.org]
evidence of autosomal recessive hypophosphatemic rickets) Metabolic workup including serum creatinine, serum phosphorus, urine phosphorus, urine creatinine, and alkaline phosphatase to evaluate for evidence of hypophosphatemic rickets by measuring [ncbi.nlm.nih.gov]
X-Ray
-
Cervical Spine X-Ray
Where endotracheal intubation is required, lateral cervical spine x-ray is recommended to evaluate for cervical spine fusion, and thereby avoid secondary complications. [orpha.net]
Thus, it seems prudent to perform a lateral cervical spine x-ray when elective endotracheal intubation is necessary, for example, prior to surgery. [ncbi.nlm.nih.gov]
Hypertrophy
-
Ventricular Hypertrophy
Electrocardiography showed left ventricular hypertrophy and strain pattern. Echocardiography showed a dilated and hypertrophied left ventricle, with bright and hyper-reflective myocardium (fig 1). Fractional shortening was 12.5%. [doi.org]
hypertrophy and multiple intracardiac as well as vascular calcifications Idiopathic arterial calcification of infancy should be suspected when there is hyperechogenicity of vessel walls, evidence of polyhydramnios or a past history of early neonatal [en.wikipedia.org]
Echocardiography demonstrated left ventricular hypertrophy with good function (fractional shortening 40%). He was normotensive. X-radiographs of chest and abdomen were normal. [documents.tips]
Repeated ECHO examinations showed normal systemic and pulmonary venous drainage, thickened semilunar and tricuspid valve leaflets, and concentric left ventricular hypertrophy. An ECG was negative for ischaemic changes. [bmcpediatr.biomedcentral.com]
Treatment
Despite treatment with disodium etidronate both children died. [doi.org]
"Generalized arterial calcification of infancy: Treatment with bisphosphonates". [en.wikipedia.org]
Treatment with bisphosphonates, which are synthetic PP(i) analogues, has been proposed as a means of reducing arterial calcifications in GACI patients, but no formalized treatment approach exists. [ncbi.nlm.nih.gov]
Treatment of hypophosphatemic rickets involves calcitriol and oral phosphate supplements. It seems prudent to avoid the use of warfarin if possible. [orpha.net]
Prognosis
Prognosis Prognosis is poor; most infants die from myocardial infarction within the first year of life, with the greatest number of deaths occurring within the first six months. [orpha.net]
The prognosis is extremely poor, with 85% of affected infants dying within the first 6 months of life. [ncbi.nlm.nih.gov]
Prognosis - Generalized arterial calcification of infancy-1 (GACI1) Not supplied. Treatment - Generalized arterial calcification of infancy-1 (GACI1) Not supplied. Resources - Generalized arterial calcification of infancy-1 (GACI1) Not supplied. [checkorphan.org]
Etiology
Idiopathic infantile arterial calcification is a disorder of unknown etiology manifested by widespread arterial calcification. This usually leads to early death from coronary artery occlusion. [ncbi.nlm.nih.gov]
Abstract Idiopathic infantile arterial calcification (IIAC) is a rare disease of unknown etiology, which causes wide-spread arterial calcification and usually leads to early death from coronary arterial occlusion. [doi.org]
Epidemiology
Summary Epidemiology Approximately 300 cases have been reported worldwide in the medical literature. The prevalence is unknown; however, based on carrier frequency of the recognized pathogenic variants, the frequency of 1/566,000 has been suggested. [orpha.net]
Pathophysiology
[…] biochemistry of nutrition 180 Nutritional disorders and their management 200 Clinical biochemistry of the gastrointestinal tract 214 Assessment of hepatic function and investigation of jaundice 231 Acute and chronic liver disease 250 Glucose metabolism and the pathophysiology [books.google.com]
It can therefore be hypothesized that the pathophysiology of ENPP1 and ABCC6 related disorders is based on common downstream mechanisms. [frontiersin.org]
Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (GACI, ACDC, and PXE, respectively), in which premature onset arterial calcification is a prominent but not sole [circresearch.com]
Inorganic pyrophosphate generation and disposition in pathophysiology. Am J Physiol Cell Physiol. 2001 ; 281 : C1–C11. Medline Google Scholar 17 Meradji M, de Villeneuve VH, Huber J, de Bruijn WC, Pearse RG. [doi.org]
Prevention
Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. [ncbi.nlm.nih.gov]
Prevention - Generalized arterial calcification of infancy-1 (GACI1) Not supplied. [checkorphan.org]
Recently, a study on animal model has described that bisphosphonate treatment may be beneficial by a dual effect for preventing ectopic soft tissue mineralization while correcting decreased bone mineralization in GACI caused by ENPP1 mutations. [iofbonehealth.org]
Alternatively, a lack of functioning MRP6 may impair the transport of a substance that would normally prevent mineralization, leading to the abnormal accumulation of calcium characteristic of GACI. [ghr.nlm.nih.gov]
Citing Literature Number of times cited according to CrossRef: 24 Yvonne Nitschke, Yan Yan, Insa Buers, Kristina Kintziger, Kim Askew and Frank Rutsch, ENPP1-Fc prevents neointima formation in generalized arterial calcification of infancy through the [doi.org]