This information is brought to you in partnership with Heart of PPA2.

Inorganic pyrophosphatase 2 deficiency – commonly known as PPA2 deficiency, or PPA2-Related Mitochondrial Disease – is a rare genetic mitochondrial disease caused by mutations in the PPA2 gene, which encodes a mitochondrial inorganic pyrophosphatase essential for cellular energy production.

PPA2 deficiency is commonly associated with sudden cardiac events, particularly in children and adolescents. In some cases, individuals may appear healthy prior to a life-threatening arrhythmia, which can be triggered by a viral illness, or alcohol exposure. Additional features reported in some individuals include cardiomyopathy, seizures, or muscle weakness, though cardiac involvement is the most consistent and serious manifestation.

Estimating the population size of PPA2 deficiency is challenging due to underdiagnosis and the possibility that some cases are misclassified as unexplained sudden cardiac death. It is considered an ultra-rare condition, with only a limited number of affected individuals and families reported in the medical literature to date.

Mutations in the PPA2 gene, which encodes a mitochondrial inorganic pyrophosphatase essential for cellular energy production.

Two broad clinical patterns have been described:

Early-onset presentation typically occurs in infancy or early childhood and may involve cardiomyopathy, lactic acidosis, and a high risk of early mortality from sudden cardiac death, often the result of a viral illness.

Later-onset presentation more commonly emerges in adolescence and is often characterized by sudden cardiac arrhythmia or sudden cardiac death, sometimes as the first recognized symptom of disease, typically following consumption of alcohol.

Because of its association with sudden cardiac death, PPA2 deficiency may first be suspected following an unexpected death in a previously healthy child or teen, with diagnosis confirmed through genetic testing of the individual or family members.

If your loved one is displaying symptoms of PPA2, their healthcare provider may order a muscle biopsy or order genetic testing to help confirm a clinical diagnosis.

We are here to help. We suggest you reach out to our Support & Education Team – online, via email at support@umdf.org or phone at (888) 900-6486 – who can suggest a host of resources including doctors, disease specific support meetings, and more. They’ll also connect you with a UMDF ambassador, a fellow PPA2 patient or family member if possible, who can help support and guide you through your questions.

• Get Support
  Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.

• Check our clinical trials finder
  Use our Clinical Trials Finder tool to see if you qualify for any clinical trials.

• Join our patient registry, mitoSHARE
  We are actively recruiting PPA2 families to participate in our patient registry, mitoSHARE. Patient registries like mitoSHARE are an integral part in charting a course toward treatments and cures for PPA2 and other mitochondrial diseases. Next generation patient registries like mitoSHARE are an integral part of expanding that number. Click here to join.

• Become an advocate
  Ask your representatives to prioritize mitochondrial disease research and support via the UMDF Advocacy Center. We’ll send regular action items so you – and your friends and family – can let Congress know where we need their support. Click here to sign up.

• Join the conversation online
  – UMDF Social Media Support Groups: Facebook Support Group
  – UMDF News & Updates: Facebook | Twitter | Instagram | YouTube

• Get involved
  Join the fight by giving your voice, generosity, time, or energy. Click here to see how you can help.

UMDF is helping chart a path toward treatments and eventual cure of mitochondrial diseases like PPA2 through:

• Research & Funding: UMDF has provided more than $15 million in research funding to find treatments for diseases like PPA2 . UMDF advocacy has helped secure an additional $70 million in federal funding via the Department of Defense and National Institutes of Health.
• Data: Over two decades ago, UMDF pioneered patient registries for the mitochondrial disease community. Today, our next generation patient registry, mitoSHARE, is helping chart a path toward the treatment and eventual cure of mitochondrial diseases.
• Patient Support: Thousands of families just like you depend upon UMDF for support and education on diseases like PPA2. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for families.
• Clinician Support: To help educate clinicians on diseases like PPA2 , we feature monthly Bench to Bedside clinician seminars, host the annual Mitochondrial Medicine Symposium, support the Mitochondrial Care Network, and educate clinicians on our Mito U platform.
• Virtual Conference: In February 2026, UMDF cohosted the first ever PPA2-focused scientific and medical conference, held virtually. You can find the recording on our YouTube page.

• Heart of PPA2

UMDF is here to help. Contact the Support Line at (888) 900-6486 weekdays from 8:00am to 5:00pm EST to connect with our Patient Concierge. Or, via email contact  support@umdf.org.