Generalised Arterial Calcification in Infants: Symptoms

Generalised arterial calcification of infancy (GACI) is a rare genetic disorder characterized by abnormal calcium deposits in the arteries, leading to severe vascular damage.

This condition is significant due to its impact on the cardiovascular system, especially in infants and young children. GACI has a low prevalence rate, affecting approximately 1 in every 200,000 births.

The calcification in the arteries can have detrimental effects on various aspects of health, including kidney function.

The kidneys play a crucial role in the body's overall function by filtering waste and excess fluids, regulating blood pressure, producing hormones like erythropoietin, and maintaining electrolyte balance. In GACI, the abnormal calcium deposits can affect these essential functions.

Over time, the calcification can impair the kidneys' ability to filter blood efficiently, leading to kidney dysfunction. This dysfunction can result in electrolyte imbalances, high blood pressure, and reduced hormone production, impacting the body's overall health.

Untreated GACI poses both short-term and long-term health risks. In the short term, kidney dysfunction can lead to fluid retention, electrolyte abnormalities, and high blood pressure, which can be life-threatening in severe cases.

In the long term, untreated GACI can progress to end-stage renal disease, requiring dialysis or kidney transplant.

The asymptomatic nature of GACI in its early stages underscores the importance of early detection through regular screenings to initiate timely interventions and prevent irreversible kidney damage.

Causes of Generalised Arterial Calcification of Infancy

The primary causes of GACI stem from genetic mutations that disrupt the body's normal calcium regulation mechanisms, leading to abnormal calcification in the arteries.

• Genetic mutations affecting enzymes involved in calcium metabolism can lead to abnormal calcium deposition in the arteries, gradually impacting kidney function over time.
• Mutations in genes associated with vascular smooth muscle cells can trigger pathological changes in the arterial walls, promoting calcification and compromising vascular health.
• Specific genetic mutations, such as those affecting the ENPP1 gene, have been linked to GACI, highlighting the genetic basis of this condition.
• Risk factors such as prematurity, low birth weight, and genetic predisposition can increase the likelihood of developing GACI.

Secondary risk factors or lifestyle contributors may include:

• Excessive intake of calcium supplements or vitamin D may exacerbate the abnormal calcification process.
• Poor dietary habits high in phosphorus or sodium can further burden the kidneys and contribute to disease progression.
• Lack of physical activity and sedentary lifestyle may impact overall cardiovascular health and increase the risk of vascular calcification.

Symptoms of Generalised Arterial Calcification of Infancy

Symptoms of GACI can vary depending on the disease progression, categorized into early-stage and advanced-stage symptoms.

• Fatigue and weakness due to reduced kidney function can impact daily activities and energy levels.
• Vague symptoms like poor feeding or irritability in infants may be misunderstood or overlooked, delaying diagnosis.

Advanced symptoms of GACI may manifest as:

• Severe hypertension and heart failure can significantly affect physical and emotional well-being, requiring immediate medical attention.
• Developmental delays or failure to thrive in infants may signal advanced disease progression and the need for intensive care.

Diagnosis of Generalised Arterial Calcification of Infancy

The diagnostic process for GACI typically involves a series of tests to confirm the presence of arterial calcification and assess kidney function.

• Genetic testing to identify specific mutations associated with GACI and confirm the diagnosis.
• Imaging studies like ultrasound or CT scans can visualize arterial calcification and assess the extent of vascular damage.
• Kidney function tests, including blood and urine analyses, help evaluate renal function and electrolyte balance.
• Biopsy may be performed to obtain tissue samples for detailed examination of calcified arteries and confirm the diagnosis.

Treatment Options for Generalised Arterial Calcification of Infancy

Treatment strategies for GACI aim to manage symptoms, slow disease progression, and preserve kidney function.

• Medications: Phosphate binders and calcimimetics may be prescribed to regulate calcium levels and prevent further calcification.
• Dietary modifications: Limiting dietary phosphorus and sodium intake can help reduce the burden on the kidneys and slow disease progression.
• Physical activity: Regular exercise can support cardiovascular health, improve blood flow, and promote overall well-being in patients with GACI.

Advanced treatments for severe cases of GACI may include:

• Dialysis: Hemodialysis or peritoneal dialysis may be necessary to manage end-stage renal disease and support kidney function.
• Kidney transplant: In cases of advanced kidney failure, a kidney transplant may be considered to restore renal function and improve quality of life.