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Generalized Arterial Calcification of Infancy

Idiopathic Infantile Arterial Calcification


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]
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]
Falling
  • Metabolism, Children's National Health System, Washington, District of Columbia. 3 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. 4 Pediatric Specialists, Avera Medical Group, Sioux Falls[ncbi.nlm.nih.gov]
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]
Tachypnea
  • Decreased fetal activity Gestation with an antenatal diagnosis of hydrops fetalis Polyhydramnios Low biophysical profile Marked cyanosis Edema Severe hypertension No or fade pulses Refusal of feeds Tachypnea Vomiting Abdominal distension General arterial[en.wikipedia.org]
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 sudden onset of fever, 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, and edema.[orpha.net]
  • Decreased fetal activity Gestation with an antenatal diagnosis of hydrops fetalis Polyhydramnios Low biophysical profile Marked cyanosis Edema Severe hypertension No or fade pulses Refusal of feeds Tachypnea Vomiting Abdominal distension General arterial[en.wikipedia.org]
Abdominal Distension
  • Decreased fetal activity Gestation with an antenatal diagnosis of hydrops fetalis Polyhydramnios Low biophysical profile Marked cyanosis Edema Severe hypertension No or fade pulses Refusal of feeds Tachypnea Vomiting Abdominal distension General arterial[en.wikipedia.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]
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]
Intracranial Hemorrhage
  • Early neonatal death occurred due to primary intracranial hemorrhage. Postmortem and genetic testing confirmed a novel mutation in the ENPP1 gene.[ncbi.nlm.nih.gov]
Amenorrhea
  • A 26 year old woman, gravida 2, para 1 with no living child, with 20 weeks amenorrhea came for antenatal check up to our clinic. Her previous pregnancy was full term normal delivery and baby died at 11 th month of age, reasons not being clear.[ojhas.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.[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]

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]
Sex distribution
Age distribution

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]

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