Arterial calcification due to CD73 deficiency

Arterial calcification due to CD73 deficiency (ACDC) is a rare genetic disorder characterized by the abnormal accumulation of calcium deposits in the arteries, particularly affecting the lower extremities. This condition is caused by mutations in the NT5E gene, which encodes the enzyme CD73. CD73 is crucial for the production of adenosine, a molecule that plays a significant role in inhibiting vascular calcification.

Pathophysiology

The NT5E gene provides instructions for making the enzyme CD73, which is involved in the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine is a signaling molecule that helps regulate blood flow and prevents calcification in the vascular system. In individuals with ACDC, mutations in the NT5E gene lead to a deficiency of CD73, resulting in reduced levels of adenosine. This deficiency disrupts normal vascular function and promotes the deposition of calcium in the arterial walls.

Clinical Features

Patients with ACDC typically present with symptoms in adulthood, often in their 30s or 40s. The primary clinical manifestations include intermittent claudication, pain in the legs due to reduced blood flow, and calcification of the arteries in the lower limbs. Over time, this can lead to significant morbidity due to impaired circulation and increased risk of cardiovascular events.

Genetics

Autosomal recessive inheritance pattern

ACDC is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. Carriers, who have only one copy of the mutation, typically do not show symptoms.

Diagnosis

The diagnosis of ACDC is based on clinical evaluation, family history, and genetic testing to identify mutations in the NT5E gene. Imaging studies, such as X-rays or CT scans, can reveal the extent of arterial calcification.

Management

Currently, there is no cure for ACDC, and treatment focuses on managing symptoms and preventing complications. This may include medications to improve blood flow, pain management, and lifestyle modifications such as exercise and diet. In some cases, surgical interventions may be necessary to restore circulation.

Research Directions

Ongoing research is focused on understanding the molecular mechanisms underlying ACDC and exploring potential therapeutic approaches. Gene therapy and pharmacological agents that can increase adenosine levels or mimic its effects are areas of active investigation.

Related Pages

• Vascular calcification
• Genetic disorders
• Adenosine
• Autosomal recessive disorder

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