What are the symptoms? The onset of GACI may be either during the fetal period, neonatal period or later in infancy. The condition is usually fatal within the first year of life but a few individuals with the condition have survived into later childhood, or more rarely into adulthood. Longer survival is sometimes related to co-existence of a condition called hypophosphataemia (a condition in which a chemical called phosphate is present at lower than normal levels in the blood stream). Before birth, affected babies may develop heart failure resulting in impaired growth, hydrops fetalis (abnormal fluid accumulation) and sometimes stillbirth. At birth, affected babies show a sudden onset of feeding abnormalities followed by breathing problems and a rapid progression to death, which usually occurs before six to nine months as a result of intractable heart failure. Pre-term infants may have more severe and rapidly advancing symptoms than full-term infants. When GACI occurs in late infancy, complications may include severe systemic hypertension (high blood pressure) and cardiomyopathy (see entry Cardiomyopathies in Children). What are the causes? GACI is a genetic condition. The gene affected in this condition is called ENPP1. This gene provides the basic instructions within the cell for manufacture of an enzyme called ecto-nucleotide pyrophosphatase/phosphodiesterase 1. This enzyme generates inorganic phosphate, which inhibits the formation of a particular type of crystal called hydroxyapatite. When the enzyme is deficient (as in GACI) there is a deficiency of inorganic phosphate and as a result calcium hydroxyapatite crystals deposit in the arteries. How is it diagnosed? In typical cases, the diagnosis will be suggested by the clinical problems. X-rays may identify calcification. Before birth, antenatal ultrasound may identify abnormalities suggestive of calcification. In the event of stillbirth or death of a child prior to a diagnosis being made, characteristic findings may be found on post-mortem examination. The diagnosis can be confirmed by genetic testing for mutation in ENPP1 gene. How is it treated? Sadly, there is no curative treatment for GACI. A particular type of medication, called bisphoshonates, have been used to treat the condition in a small number of babies/children. Some have been found to have gradual disappearance of calcification when treated with bisphosphonates but others have died despite this treatment. Very occasionally, infants affected with the condition have been reported to have resolution of the calcification without any treatment. The use of bisphosphonates to treat GACI therefore remains uncertain. Inheritance patterns and prenatal diagnosis Inheritance patternsGACI is inherited as an autosomal recessive trait. Prenatal diagnosisPrenatal diagnosis is possible on routine ultrasound by observing areas within the major blood vessels that transmit stronger echoes than surrounding tissue. When cardiomyopathy and polyhydramnios (excess of amniotic fluid), are present prenatally, careful evaluation for calcification is prudent. Fetal heart failure may result in polyhydramnios, fetal hydrops (gross swelling of the fetus), and/or fetal death. If there is a family history of GACI, the condition can be screened for in subsequent pregnancies by genetic testing for mutations in ENPP1 following amniocentesis or chorionic villus sampling or by serial antenatal ultrasound scans to detect fetal hydrops. Is there support? GACI Global Tel: +353-87-244-4488Email: [email protected]Website: gaciglobal.org GACI Global is a nonprofit organization whose mission is to connect families affected by Generalized Arterial Calcification of Infancy or Hypophosphatemic Rickets caused by ENPP1or ABCC6 Deficiencies to each other and to the medical community. The organization strives to provide current educational resources and supports ongoing research. Their goal is to provide information about what complications can occur due to ENPP1 and ABCC6 Deficiencies (e.g. GACI, ARHR2) and to provide hope for families impacted by the condition. They hope that their website, newsletter, and social media outlets act as a resource not only for medical information, but for personal support during your own GACI/ARHR2 journey. Their community is small, but growing and they hope to offer support and information to families affected by this disorder around the world. Group details added October 2019
What are the symptoms? The onset of GACI may be either during the fetal period, neonatal period or later in infancy. The condition is usually fatal within the first year of life but a few individuals with the condition have survived into later childhood, or more rarely into adulthood. Longer survival is sometimes related to co-existence of a condition called hypophosphataemia (a condition in which a chemical called phosphate is present at lower than normal levels in the blood stream). Before birth, affected babies may develop heart failure resulting in impaired growth, hydrops fetalis (abnormal fluid accumulation) and sometimes stillbirth. At birth, affected babies show a sudden onset of feeding abnormalities followed by breathing problems and a rapid progression to death, which usually occurs before six to nine months as a result of intractable heart failure. Pre-term infants may have more severe and rapidly advancing symptoms than full-term infants. When GACI occurs in late infancy, complications may include severe systemic hypertension (high blood pressure) and cardiomyopathy (see entry Cardiomyopathies in Children).
What are the causes? GACI is a genetic condition. The gene affected in this condition is called ENPP1. This gene provides the basic instructions within the cell for manufacture of an enzyme called ecto-nucleotide pyrophosphatase/phosphodiesterase 1. This enzyme generates inorganic phosphate, which inhibits the formation of a particular type of crystal called hydroxyapatite. When the enzyme is deficient (as in GACI) there is a deficiency of inorganic phosphate and as a result calcium hydroxyapatite crystals deposit in the arteries.
How is it diagnosed? In typical cases, the diagnosis will be suggested by the clinical problems. X-rays may identify calcification. Before birth, antenatal ultrasound may identify abnormalities suggestive of calcification. In the event of stillbirth or death of a child prior to a diagnosis being made, characteristic findings may be found on post-mortem examination. The diagnosis can be confirmed by genetic testing for mutation in ENPP1 gene.
How is it treated? Sadly, there is no curative treatment for GACI. A particular type of medication, called bisphoshonates, have been used to treat the condition in a small number of babies/children. Some have been found to have gradual disappearance of calcification when treated with bisphosphonates but others have died despite this treatment. Very occasionally, infants affected with the condition have been reported to have resolution of the calcification without any treatment. The use of bisphosphonates to treat GACI therefore remains uncertain.
Inheritance patterns and prenatal diagnosis Inheritance patternsGACI is inherited as an autosomal recessive trait. Prenatal diagnosisPrenatal diagnosis is possible on routine ultrasound by observing areas within the major blood vessels that transmit stronger echoes than surrounding tissue. When cardiomyopathy and polyhydramnios (excess of amniotic fluid), are present prenatally, careful evaluation for calcification is prudent. Fetal heart failure may result in polyhydramnios, fetal hydrops (gross swelling of the fetus), and/or fetal death. If there is a family history of GACI, the condition can be screened for in subsequent pregnancies by genetic testing for mutations in ENPP1 following amniocentesis or chorionic villus sampling or by serial antenatal ultrasound scans to detect fetal hydrops.
Is there support? GACI Global Tel: +353-87-244-4488Email: [email protected]Website: gaciglobal.org GACI Global is a nonprofit organization whose mission is to connect families affected by Generalized Arterial Calcification of Infancy or Hypophosphatemic Rickets caused by ENPP1or ABCC6 Deficiencies to each other and to the medical community. The organization strives to provide current educational resources and supports ongoing research. Their goal is to provide information about what complications can occur due to ENPP1 and ABCC6 Deficiencies (e.g. GACI, ARHR2) and to provide hope for families impacted by the condition. They hope that their website, newsletter, and social media outlets act as a resource not only for medical information, but for personal support during your own GACI/ARHR2 journey. Their community is small, but growing and they hope to offer support and information to families affected by this disorder around the world. Group details added October 2019