PPA2 Awareness Day Date in the current year: May 2, 2025

Inorganic pyrophosphatase is an enzyme that catalyzes the conversion of one pyrophosphate ion into two phosphate ions. The functionality of pyrophosphatase plays an important role in several biological processes, including lipid metabolism, DNA and RNA polymerization, and calcium absorption. The enzyme is encoded by two genes, PPA1 on chromosome 10 and PPA2 on chromosome 4.

Mutations in the PPA2 gene can cause a very rare disorder called PPA2 deficiency. Inorganic pyrophosphatase 2, encoded by the PPA2 gene, is responsible for breaking down pyrophosphate in mitochondria, the organelles that provide chemical energy to cells. When PPA2 doesn’t work properly, pyrophosphate accumulates in the mitochondria, disrupting their normal function and causing energy depletion and cell damage. PPA2 deficiency is particularly dangerous for energy-demanding organs and systems, such as the heart and nervous system.

Symptoms of PPA2 deficiency depend on the specific mutation in the PPA2 gene and can range from mild to severe. Some forms appear in infancy or childhood, while others may manifest later in life, in adolescence or early adulthood. PPA2 can cause:

• Neurological symptoms (developmental delay, seizures, ataxia)
• Muscle weakness
• Cardiomyopathy (heart muscle disease)
• Sudden cardiac arrest (often triggered by infection, physical exertion, alcohol consumption, and other stressors)

PPA2 deficiency is usually suspected in children and young adults who experience sudden cardiac events such as arrhythmia or cardiac arrest. The most definitive way to confirm the diagnosis is through genetic testing. Treatment usually focuses on preventing life-threatening cardiac events with medications, avoiding known triggers, and implanting an ICD in patients at high risk for sudden cardiac arrest.

PPA2 deficiency is a very dangerous condition because it can cause serious health problems or even sudden death before it is properly diagnosed. In severe cases, patients with PPA2 deficiency require intensive and continuous medical care. The situation is exacerbated by the extreme rarity of the condition, which means that many patients and their families do not have access to the resources and support they need.

PPA2 Awareness Day was created in 2025 to raise awareness of PPA2 deficiency, promote research, and support patients and their families. It is organized by Heart of PPA2, a nonprofit organization that raises awareness of PPA2, advocates for research, and brings together patients, their families, and caregivers from around the world to show them they are not alone.

You can get involved with PPA2 Awareness Day by learning more about this rare genetic disorder and sharing what you’ve learned with others, donating to Heart of PPA2, and spreading the word on social media using the hashtag #PPA2AwarenessDay.