Introduction:
Generalized arterial calcification occurs genetically from parents carrying defective genes. It can be present in two forms. Most of the symptoms are related to affecting the condition of the heart due to the blockage of blood vessels by the deposition of calcium in them. This condition occurs in infants, and the condition can be diagnosed before birth through ultrasound and even after birth by various imaging techniques. This article explains the causes, forms, and treatment of this condition.
What Is Generalized Arterial Calcification of Infancy?
Generalized arterial calcification of infancy is a rare genetic disorder that affects the circulatory system. The disease causes an abnormal increase in the calcium-binding up in the walls of the blood vessels that supply even the heart and the entire body. It occurs during the development of the fetus. Calcium build-up occurs due to genetic defects, which cause decreased levels of pyrophosphate. This pyrophosphate prevents the deposition of calcium in the blood vessels. Calcium starts to build up due to a lack of pyrophosphate, which hardens the blood vessels in newborns and shows hypertension, kidney disease, and heart disease at birth.
What Are the Causes of Generalized Arterial Calcification in Infancy (GACI)?
It is a genetic condition, and it is characterized into two forms. Both of them are autosomal recessive, which are inherited by two defective genes.
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Type 1: It is the most common form of GACI, which affects almost two-thirds of the individuals with ENPP1 gene mutation. This gene helps in the preparation of pyrophosphate. Defects in the gene lead to alteration in the levels of pyrophosphate, which in turn leads to calcium deposition.
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Type 2: This form is caused by the ABCC6 gene mutation. This also leads to decreased levels of pyrophosphate, which affects the skin, eyes, and cardiovascular systems.
What Are the Symptoms of Generalized Arterial Calcification in Infancy?
The condition occurs mostly in infants and is characterized by arterial calcification or constricting of large and medium-sized blood vessels that result in cardiovascular findings heart failure, edema (accumulation of fluid causing swelling), and cyanosis (bluish discoloration of the skin). Other clinical symptoms include eye and skin manifestations, blood vessel calcifications, the fusion of the cervical spine along with hearing loss. While the mortality rate of infants is high, existence into the third and fourth decades occurs with much difficulty.
What Are the Diagnostic Criteria for Generalized Arterial Calcification in Infancy?
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Diagnosis is obtained at an early stage in almost half of all newborns.
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Clinical symptoms after birth, such as high blood pressure, heart failure, and difficulty in respiration or fluid collection, can also point out the presence of GACI.
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Imaging techniques also depict the presence of arterial calcifications.
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Computer tomography helps in assessing the calcification along with the thickening of the internal layer of the blood vessel.
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Ultrasound examination of the head and the abdomen detects the presence of alterations in blood vessels as bright vessels.
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Magnetic resonance images detect blockage in the arterial wall. It works similar to that of angiography.
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Plain radiographs detect calcifications, but generally with decreased sensitivity, and mostly, they can be detected only by re-examination of the X-ray after confirmation of the diagnosis through other tests.
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Confirmation of the diagnosis for any genetically associated syndrome or disorder is done by molecular genetic testing, which includes comprehensive genomic tests and gene-targeted testing.
What Is the Treatment Plan for Generalized Arterial Calcification in Infancy?
Treatment of Manifestations:
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Medication targeting the cells that show the impact on calcium build-up and mineralization are used.
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Bisphosphonates (drugs to treat osteoporosis) are used to treat children diagnosed with GACI after birth.
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Most of the accepted treatment interventions are started at an early stage as calcium starts to build up during the early developmental stages.
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When the condition is diagnosed before birth by an ultrasound, prenatal treatment is opted for. Medications for treating osteoporosis are given to the mother in the third trimester, which helps stop calcium buildup in the blood vessels of the fetus.
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Standard anti-hypertensive therapy is needed for treating hypertension.
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Aspirin therapy is required in individuals suffering from severe coronary stenosis (narrowing of coronary arteries).
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Intravitreal VEGF inhibitors are necessary for choroidal neovascularization (abnormal growth or production of blood vessels in a part of the eye).
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Supplements of oral phosphates and calcitriol are used in treating hypophosphatemic rickets (a condition caused by defective mineralization of the bone)
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Hearing aids (if advised, when needed) are all used in managing the disorder.
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Children often tend to have heart or kidney disease, which requires long-term treatment and care. Based on the symptoms and clinical condition, an interprofessional team consisting of cardiologists, nephrologists, and other physicians monitor and treat the condition. Treatment and follow-up also depend on the type of the condition.
Surveillance and Follow-Up Care:
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There is no certain procedure or guideline for surveillance. The frequency of each follow-up also depends on the clinical condition of the individual.
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Monitoring of arterial calcifications can be done by undergoing a low-dose computed tomography (CT) scan every three to four months in the first year after treatment.
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Examination of the retina can be done yearly, along with laboratory tests, to determine the balance in the levels of minerals present in the blood.
Evaluation of Relatives at Risk:
It is necessary to evaluate the younger siblings of individuals with GACI to predict the presence of the disorder as early as possible to obtain benefit from the treatment and to follow certain preventive measures.
The following evaluations are included:
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Molecular Genetic Testing: It is a type of confirmatory genetic testing that should be done if the pathogens causing the disorder in the family are already known.
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Imaging Studies: Digital visualization of the internal organs can be done in cases where the causative agents are unknown.
What Is Genetic Counseling?
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Genetic counseling is provided by a geneticist to help the patient and their family members make appropriate decisions in dealing with genetic disorders.
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It is a process where all the information related to the genetic disorder, like the nature, cause, and mechanism of the pathology, are explained to the patient.
Conclusion
Generalized arterial calcification in infants can cause serious effects on the overall metabolism of the infant as well as alteration of functions in various organ systems. Symptomatic treatment is given in most cases. Early treatment intervention after birth or before birth helps in improved treatment outcomes. Treatment before birth is called prenatal treatment, which is provided by the mother to the infant. Risk assessment of the disorder in the family is important to prevent the disease and also to overcome future complications.
