[en.wikipedia.org] [symptoma.com] Case presentation The clinical presentation was characterized by a severe early-onset of hypertension refractory to multiple therapy. [symptoma.com]

However, rare cases with later presentations have been reported [1, 3]. Without appropriate treatment, IIAC has a high morbidity and mortality rate. [hindawi.com]

Case Presentation An un-booked 29 years old mother in the 32-week gestation, from a consanguineous marriage, was presented to our obstetric clinic for further evaluation of polyhydramnios. [avensonline.org]

• Pain

  […] bone pain, bowed femora, and short stature. [symptoma.com]

  […] the child uses for pain, e.g., ouch, hurt. • Ask the child to give examples of pain (to identify the child’s understanding and use of words Chest Wall Pain: Costochondritis. [apotechsrl.it]

  Beyond six months, the mortality rate significantly decreases among survivors, who may later develop ARHR2, characterized clinically by short stature, bone deformities and pain. [bone-abstracts.org]

  At first, she began having pain in her hands and was initially diagnosed with arthritis. However, test results were negative. She was sent home with no answers. Over the years, the pain intensified and traveled to her lower extremities. [medicalbag.com]

  Rickets leads to severe skeletal deformities, short stature, severe bone pain, and an increased risk of bone fractures. [inozyme.com]

• Inflammation

  [rareguru.com] Inflammation However, inflammation suggestive of myocarditis could not be identified (Figures 2(b) and 2(c)). [hindawi.com] Thus RAGE and S100A12 pathway are broadly tied to inflammation and vascular disease. [symptoma.com]

  However, inflammation suggestive of myocarditis could not be identified (Figures 2(b) and 2(c)). [hindawi.com]

  Thus RAGE and S100A12 pathway are broadly tied to inflammation and vascular disease. [ncbi.nlm.nih.gov]

  Atherosclerotic factors such as lipid oxidation and inflammation play roles that have not yet been fully elucidated. [news-medical.net]

• Congestive Heart Failure

  […] with symptoms of congestive heart failure. [symptoma.com]

  Patients with GACI suffer from hypertension, severe myocardial ischemia, and congestive heart failure and often die within 6 months of life. On the other end, PXE is associated with considerable morbidity, rarely with mortality. [moh-it.pure.elsevier.com]

  The cause of death is frequently myocardial infarction or stroke, and hypertension and congestive heart failure are common in fetuses and infants with GACI. [clinicaltrials.gov]

  Presentation of late-onset disease variably includes respiratory distress, cyanosis, feeding difficulties, congestive heart failure, vomiting, irritability, failure to thrive, fever, hypertension, and edema. [rareguru.com]

• Plethora

  [bmcpediatr.biomedcentral.com] Plethora Chest radiography showed cardiomegaly and pulmonary plethora. Electrocardiography showed left ventricular hypertrophy and strain pattern. [symptoma.com]

  These factors may be broadly categorized into two major causes, namely, an elevated calcium blood level (hypercalcemia) and tissue injury, both of which may be triggered by a plethora of conditions. [news-medical.net]

  Extramedullary hematopoiesis of liver [9] Hypertrophy of myocardium Bright and hyper-reflective myocardium[10] Periarticular calcifications in the wrists, ears, shoulders, ankles and hip[11][12] Heart usually looks structurally normal Cardiomegaly and pulmonary plethora [wikidoc.org]

• Weakness

  [webmd.com] Weakness At one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his examination was normal. [symptoma.com]

  In the adult phase, in addition to continuing vascular and organ calcification, ENPP1 deficiency manifests as osteomalacia, which leads to severe bone pain, fatigue, muscle weakness, and risk of recurring bone fractures. [inozyme.com]

  Symptoms of a stroke include sudden weakness, confusion, or dizziness, along with vision and speech impairment. [share.upmc.com]

  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. [bone-abstracts.org]

• Respiratory Distress

  respiratory [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. [symptoma.com]

  Early-onset disease presents variably with fetal distress, heart failure, polyhydramnios, hypertension, respiratory distress, hydrops fetalis, edema, visceral effusions, cyanosis, cardiomegaly, and ascites. [rareguru.com]

  We report a 4-week-old neonate who initially presented with respiratory distress, heart failure, and Coxsackie B viremia suggestive of viral induced cardiomyopathy. [hindawi.com]

• Tachypnea

  [acc.org] Tachypnea [apotechsrl.it] Tachypnea [symptoma.com] Tachypnea [bone-abstracts.org] Tachypnea […] months of life or in utero. [2] Decreased fetal activity Gestation with an antenatal diagnosis of hydrops fetalis [6] [7] Polyhydramnios Low biophysical [symptoma.com]

  […] or in utero.[2] History and Symptoms Decreased fetal activity Gestation with an antenatal diagnosis of hydrops fetalis[3][4] Polyhydramnios Low biophysical profile Marked cyanosis Edema[5] Severe hypertension[6] No or fade pulses Refusal of feeds[7] Tachypnea [wikidoc.org]

  She had tachycardia (heart rate 180/min), tachypnea (respiratory rate 80/min) with normal blood pressure and required supplemental oxygen. Peripheral pulses were not palpable. Systemic examination was normal. [pediatriconcall.com]

• Dyspnea

  [rareguru.com] Dyspnea [orpha.net] Dyspnea [unboundmedicine.com] Dyspnea In GACI probands, initial symptoms included dyspnea (62%) and cyanosis (16%); 73% were ventilated. [symptoma.com]

  In GACI probands, initial symptoms included dyspnea (62%) and cyanosis (16%); 73% were ventilated. [bone-abstracts.org]

  Initially, she had dyspnea consistent with New York Heart Association (NYHA) Functional Classification class II (light limitation of physical activity with ordinary physical activity resulting in fatigue, palpitation, dyspnea) which progressed to class [cureus.com]

  Color compare parasternal short axis view demonstrating origin of the right coronary artery from the left sinus of Valsalva in a 16-year-old female presenting with exertional chest pain and dyspnea. [acc.org]

• Vomiting

  [contact.org.uk] Vomiting [orpha.net] [orpha.net] Vomiting Of these, 48% of cases presented in utero or at birth with hydrops fetalis, maternal hydramnios, heart failure, or respiratory distress and 52% present later, at a median age of 3 months, with [symptoma.com]

  Presentation of late-onset disease variably includes respiratory distress, cyanosis, feeding difficulties, congestive heart failure, vomiting, irritability, failure to thrive, fever, hypertension, and edema. [orpha.net]

  […] utero.[2] History and Symptoms Decreased fetal activity Gestation with an antenatal diagnosis of hydrops fetalis[3][4] Polyhydramnios Low biophysical profile Marked cyanosis Edema[5] Severe hypertension[6] No or fade pulses Refusal of feeds[7] Tachypnea Vomiting [wikidoc.org]

• Abdominal Distension

  Distension Distension [en.wikipedia.org] [en.wikipedia.org] The infant’s subsequent course in NICU was complicated by recurrent abdominal distension, feeding intolerance, irritability, pyrexia and systemic hypertension. [symptoma.com]

  distension General arterial rigidity[8] Cardiac failure (most common clinical finding) Strain pattern Dilated and hypertrophied ventricles Extramedullary hematopoiesis of liver [9] Hypertrophy of myocardium Bright and hyper-reflective myocardium[10] [wikidoc.org]

  The infant’s subsequent course in NICU was complicated by recurrent abdominal distension, feeding intolerance, irritability, pyrexia and systemic hypertension. Oral Editronate Sodium (10 mg/kg/day, twice a day) was started on day 40. [bmcpediatr.biomedcentral.com]

• Failure to Thrive

  […] to Thrive Idiopathic infantile arterial calcification was diagnosed in a 2 week old infant with failure to thrive associated with neurological, renal and cardiac signs. [symptoma.com]

  Presentation of late-onset disease variably includes respiratory distress, cyanosis, feeding difficulties, congestive heart failure, vomiting, irritability, failure to thrive, fever, hypertension, and edema. [orpha.net]

  The features associated with GACI typically include heart failure, hypertension (high blood pressure), and failure to thrive. These features vary, with each infant being differently affected by the severity of their symptoms. [contact.org.uk]

• Hepatosplenomegaly

  [bmcpediatr.biomedcentral.com] Liver, Gall & Pancreas Hepatosplenomegaly […] clinical features including microcephaly, intracranial calcifications, rash, intrauterine growth restriction, jaundice, hepatosplenomegaly [hindawi.com] The absence of jugular [symptoma.com]

  […] calcification involving aorta, carotid, cerebral, renal, mesenteric and cardiac arteries Echo-dense aortic annulus, ascending aorta, transverse arch, descending aorta, main pulmonary artery, and coronary arteries unusually.[13] Abdominal ultrasound can reveal hepatosplenomegaly [wikidoc.org]

  Although each of the congenital intrauterine infections has distinct clinical manifestations and sequelae, some of them do share certain clinical features including microcephaly, intracranial calcifications, rash, intrauterine growth restriction, jaundice, hepatosplenomegaly [hindawi.com]

  The absence of jugular turgor and hepatosplenomegaly were evaluated and fluids were administered through intraosseous tibial as anti-shock rescue; however, the non-invasive blood pressure remains invaluable. [pediatrics.imedpub.com]

• Hypertension

  [en.wikipedia.org] [en.wikipedia.org] Anti-hypertensive therapy is warranted for hypertension. [orpha.net] At the age of 2 years the child is doing well but requires medical treatment for arterial hypertension. [symptoma.com]

  She had severe hypertension in the second week of life, with mean arterial pressures up to 90 mm Hg. Hypertension was initially managed with oral amlodipine and later on she was switched over to captopril 1.2 mg/kg/day over a period of 7 days. [pediatriconcall.com]

  IIAC may present antenatally with polyhydramnios with or without arterial calcification, and may present postnatally if intractable systemic hypertension and/or heart failure from systemic hypertension and or ischemic coronary artery disease. [avensonline.org]

  Case presentation The clinical presentation was characterized by a severe early-onset of hypertension refractory to multiple therapy. [go.gale.com]

• Heart Failure

  [pediatriconcall.com] Heart Failure [moh-it.pure.elsevier.com] Heart Failure [doi.org] Heart Failure We report the case of a 32-week-old infant with hydrops fetalis and heart failure who died at 4 days of age. [symptoma.com]

  We report the case of a 4-year-old Italian child submitted to heart transplant, at 18 months old, for end-stage heart failure due to extensive myocardial infarction of the left ventricle and diffuse coronary calcifications. [moh-it.pure.elsevier.com]

  Fetal heart failure may result in polyhydramnios, fetal hydrops (gross swelling of the fetus), and/or fetal death. [contact.org.uk]

  After birth, affected babies may show signs of heart failure, high blood pressure, respiratory distress, edema or fluid collections, or an enlarged heart. [chop.edu]

• Cyanosis

  There are 2 types: Central cyanosis and Acrocyanosis. [nicklauschildrens.org] There are 2 types: Central cyanosis and Acrocyanosis. [symptoma.com]

  Reviewed by: Jack Wolfsdorf, MD, FAAP This page was last updated on: December 18, 2020 05:03 PM Learn more about Cyanosis A bluish tinge of the lips, tongue, nail beds or skin is called cyanosis. There are 2 types: Central cyanosis and Acrocyanosis. [nicklauschildrens.org]

  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]

• Cardiomegaly

  A chest X-ray showed massive cardiomegaly and pulmonary oedema. [symptoma.com]

  Case Presentation A multigravida with previous two normal issues was referred at 36 weeks of gestation, as the screening ultrasound revealed cardiomegaly. [austinpublishinggroup.com]

  […] in affected individuals, with signs and symptoms including difficulty breathing, accumulation of fluid (edema) in the extremities, a bluish appearance of the skin or lips (cyanosis), severe high blood pressure (hypertension), and an enlarged heart (cardiomegaly [rarediseases.oscar.ncsu.edu]

• Weak Pulse

  [bmcpediatr.biomedcentral.com] Weak Pulse At one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his examination was normal. [symptoma.com]

  At one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his examination was normal. A chest X-ray showed massive cardiomegaly and pulmonary oedema. [bmcpediatr.biomedcentral.com]

• Hearing Impairment

  [ojhas.org] Ears Hearing Impairment [doi.org] Ears Hearing Impairment Fishman G, Miller-Hansen D, Jacobsen C, Singhal V, Alon U: Hearing impairment in familial X-linked hypophosphatemic rickets. Eur J Pediatr 2004;163:622-623. [symptoma.com]

• Angioid Streaks of the Retina

  Also, many PXE characteristics, including angioid streaks of the retina and peau d’orange skin lesions might frequently be overlooked in the clinical examinations of GACI patients. [frontiersin.org]

  Some case reports described association with clinical features of PXE such as angioid streaks of the retina and papular skin lesions [2]; PXE is characterized by dystrophic calcification of soft tissues. [bmcpediatr.biomedcentral.com]

• Ulcer

  [symptoma.com] Skin Ulcer Infants with GACI may suffer from gastrointestinal complications such as ulcerating inflammation of the wall of the small intestine or obstruction due to stenosis. [symptoma.com]

  Infants with GACI may suffer from gastrointestinal complications such as ulcerating inflammation of the wall of the small intestine or obstruction due to stenosis. [gaciglobal.org]

  Dystrophic calcification is also frequently noted in diseased tissue, such as chronic ulcers and granulomas as well as in benign and malignant neoplasms. [oncotarget.com]

  Surgery is indicated when lesions are painful, recurrently infected, ulcerated or when functional impairment occurs[149]. [wjgnet.com]

• Hydrops Fetalis

  [doi.org] Fetus Hydrops Fetalis We report the case of a 32-week-old infant with hydrops fetalis and heart failure who died at 4 days of age. [ncbi.nlm.nih.gov] Antenatal detection of idiopathic arterial calcification with hydrops fetalis. [symptoma.com]

  Conclusion: GACI might be one of the possible etiologies of hydrops fetalis. [thieme-connect.com]

  Nagar AM, Hanchate V, Tandon A, Thakkar H, Chaubal NG: Antenatal detection of idiopathic arterial calcification with hydrops fetalis. J Ultrasound Med 2003;22:653–659. [karger.com]

  "Antenatal Detection of Idiopathic Arterial Calcification With Hydrops Fetalis". Journal of Ultrasound in Medicine. 22 (6): 653–9. PMID 12795564. ↑ Maayan, Ch.; Peleg, O.; Eyal, F.; Mogle, P.; Rosenmann, E.; Ziv, J. Bar (1984). [wikidoc.org]

• Irritability

  vomiting, irritability, or respiratory [ncbi.nlm.nih.gov] Presentation of late-onset disease variably includes respiratory distress, cyanosis, feeding difficulties, congestive heart failure, vomiting, irritability, failure to thrive, fever, hypertension [symptoma.com]

  Presentation of late-onset disease variably includes respiratory distress, cyanosis, feeding difficulties, congestive heart failure, vomiting, irritability, failure to thrive, fever, hypertension, and edema. [orpha.net]

  Newborns with GACI may also present with feeding difficulties, irritability, or failure to thrive. In nearly 50% of cases, babies are diagnosed soon after birth due to these symptoms. [gaciglobal.org]

• Kidney Failure

  [karger.com] Urogenital Kidney Failure The initial indication of GACI is high blood pressure or kidney failure. Physicians may order X-rays for newborns with these conditions to look for calcification in arteries. [symptoma.com]

  The initial indication of GACI is high blood pressure or kidney failure. Physicians may order X-rays for newborns with these conditions to look for calcification in arteries. [chop.edu]

  […] abdomen and and kidney failure. [nicklauschildrens.org]

[orpha.net] Workup [doi.org] 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. [symptoma.com]

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. [old.jcdronline.org]

Initial working diagnosis included congenital infection; however, patients remained without a definitive diagnosis despite extensive workup. Consequently, we investigated a potential genetic etiology. [meta.org]

Laboratory workup was significant for a low serum phosphorus; elevated parathyroid hormone (PTH); elevated 1,25(OH)2D; and reduced renal tubular reabsorption of phosphorus, or TRP. [mayoclinic.org]

• Pericardial Effusion

  The sonographic examination performed at 28 weeks' gestation revealed scalp edema, severe skin edema, bilateral hydrocele, ascites, and pleural and pericardial effusion. [avesis.istanbul.edu.tr]

  [symptoma.com] X-Ray 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. [symptoma.com]

  Targeted ultrasonography revealed moderate cardiomegaly and pericardial effusion in the fetus (Figure 1). There were no structural abnormality of the heart on fetal ECHO. [austinpublishinggroup.com]

  Antenatally there was presence of pericardial effusion leading to hydrops and polyhydramnios. [pediatriconcall.com]

  Table 1: Reported cases of IIAC with pericardial effusion. [avensonline.org]

• Ventricular Hypertrophy

  [austinpublishinggroup.com] Hypertrophy Ventricular Hypertrophy Electrocardiography showed left ventricular hypertrophy and strain pattern. [symptoma.com]

  Echocardiography showed left ventricular hypertrophy and low contractility, but normal aortic arch dimensions. [bone-abstracts.org]

  […] function, however mild concentric ventricular hypertrophy and multiple intracardiac as well as vascular calcifications[3] Idiopathic arterial calcification of infancy should be suspected when there is hyperechogenicity of vessel walls, evidence ofpolyhydramnios [wikidoc.org]

  hypertrophy, and VSD [10]. [cureus.com]

Both the GACI and ARHR2 phenotypes are potentially fatal or associated with severe morbidity, with no FDA-approved drugs or proven treatments. [clinicaltrials.gov]

"Generalized arterial calcification of infancy: Treatment with bisphosphonates". [wikidoc.org]

Conclusion: Bisphosphonate therapy at present is the treatment of choice for systemic arterial involvement in GACI, and heart transplant has proven to be the definitive treatment in case with extensive myocardial infarction, as in our. [moh-it.pure.elsevier.com]

[cureus.com] Treatment 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. [symptoma.com]

Treatment with bisphosphonates is ongoing, but is planned to be discontinued at 3 years of age. The child has remained healthy and developmentally normal. [go.gale.com]

[austinpublishinggroup.com] [austinpublishinggroup.com] [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 [symptoma.com]

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]

It has a poor prognosis, with mortality been reported by the age of 4-6 months. [avensonline.org]

[orpha.net] Etiology […] cardiomyopathy as the etiology [hindawi.com] Inherited arterial calcifications syndromes: etiologies and treatment concepts. [symptoma.com]

Although Coxsackie B viremia was confirmed by PCR and presumed to be the etiology of the cardiomyopathy, microscopic sections on autopsy failed to demonstrate any evidence of inflammation and thus not supporting viral induced cardiomyopathy as the etiology [hindawi.com]

Inherited arterial calcifications syndromes: etiologies and treatment concepts. Curr Osteoporos Rep. 2017;15:255–70. CrossRefPubMed Nitschke Y, Rutsch F. Inherited arterial calcifications syndromes: etiologies and treatment concepts. [springermedizin.de]

Amorphic, chondromorphic, or osteomorphic are the classifications on a histological basis, whereas metastatic (diffuse calcification) or dystrophic (not metastatic) are used to determine etiology. [news-medical.net]

[…] the combination of polyhydramniosis and intrauterine growth restriction may necessitate examination of the major vessels for presumptive a diagnosis of IIAC. (20420290) Idiopathic infantile arterial calcification (IIAC) is a rare disease of unknown etiology [humpath.com]

[medun.acad.bg] [doi.org] Epidemiology Summary Epidemiology Approximately 300 cases have been reported worldwide in the medical literature. [symptoma.com]

Petrova Department of Epidemiology, Medical University – Sofia Summary. The purpose of this study is to present epidemiological characteristics of nosocomial outbreaks of airborne diseases in Bulgaria. [medun.acad.bg]

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]

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. [rareguru.com]

[symptoma.com] It can therefore be hypothesized that the pathophysiology of ENPP1 and ABCC6 related disorders is based on common downstream mechanisms. [symptoma.com]

Unusual features in this disease include ultrasonographic prenatal diagnosis in the second two siblings and ultrastructural studies of the third patient that might shed light on the pathophysiologic characteristics of this disease. [jamanetwork.com]

Pseudoxanthoma Elasticum: a clinical pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet 2005; 42:881-892 [PubMed] 12. OMIM: An online catalog of human genes and genetic disorders [Electronic resource]. [journal.nephrolog.ru]

Despite intensifying research and increasing awareness of these issues, the underlying pathophysiology of the vasculopathy of CKD and PXE remains mostly unknown. [karger.com]

ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nature Communications, 6. https://doi.org/10.1038/ncomms10006 [mendeley.com]

ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013;110(50):20206–11. [springermedizin.de]

[ncbi.nlm.nih.gov] Prevention - Generalized arterial calcification of infancy-1 (GACI1) Not supplied. [symptoma.com]

Secondary Prevention Cost-Effectiveness of Therapy Future or Investigational Therapies Case Studies Case #1 Idiopathic infantile arterial calcification history and symptoms On the Web Most recent articles Most cited articles Review articles CME Programs [wikidoc.org]