Studying ENPP1 Deficiency
(GACI or ARHR2)
Now enrolling patients with ENPP1 deficiency (GACI or ARHR2) in an observational study or the first clinical trial for a potential new treatment. With your participation, healthcare providers can better understand this disease. You can also help inform possible future treatment options.

Join our research!

About ENPP1 deficiency

ENPP1 deficiency is a rare and life-threatening genetic disorder caused by mutations in the ENPP1 gene1

ENPP1 deficiency leads to a low amount of pyrophosphate (PPiA substance made by the body to control mineral buildup in soft tissues)2

This causes a disease that could affect the entire body3

The time of onset and symptoms for ENPP1 deficiency vary widely3

0-12 months
Adult
Early symptoms3
  • Neointimal proliferationThickening of the artery wall due to the growth of smooth muscle and/or mineralizationBuildup of different minerals in the body of arteries and aorta within the first few months of life
Symptoms that can appear from the fetal stage through adulthood3
  • Neointimal proliferationThickening of the artery wall due to the growth of smooth muscle and/or organ mineralizationBuildup of different minerals in the body of the kidneys, heart, and brain
  • Organ dysfunction and failure of the:
    • Heart (eg, valve defect One or more valves in the heart is not working properly, reduced ejection fractionThe heart muscle is not contracting normally, leading to heart failure, and irregular heartbeat)
    • Lungs (eg, cyanosisA bluish color change in the skin, pneumonia, fluid buildup, and high blood pressure in the lungs)
    • Gastrointestinal system (eg, feeding intoleranceDifficulty with food digestion through the gut, nausea, vomiting, bleeds, bloating, constipation, and jaundice)
    • Kidneys (eg, calcium buildup)
    • Skeleton (eg, joint pain, rickets [bowed limbs], gait abnormality, and short stature)
  • Neurological symptoms (eg, developmental delay, seizure, and stroke)
  • Hearing loss
People living with ENPP1 deficiency have been diagnosed as:
  • Neointimal proliferationThickening of the artery wall due to the growth of smooth muscle and/or mineralizationBuildup of different minerals in the body and/or of the aorta, arteries, joints, and major organs (eg, heart and kidneys)
  • Organs can start to fail or not work properly
  • In the past, infants with ABCC6 deficiency have been diagnosed with GACI
    • These infants can have the same set of symptoms as those living with ENPP1 deficiency
  • Soft and deformed bones due to undermineralization
  • This can lead to severe skeletal defects, short height, bone pain, and a greater risk of bone breaks

People with ENPP1 deficiency have a high risk of death early in life. Those who survive face many health issues.3 If you think that you may have ENPP1 deficiency but your diagnosis has not been confirmed, consider getting a no‑charge genetic test to verify.

The ENPP1 Deficiency Prospective Observational Study

The ENPP1 Prospective Observational Study is designed to look at how ENPP1 deficiency presents and progresses from birth through adulthood. The study will include people across all age groups. Researchers will follow participants over time to:
  • Map the course of ENPP1 deficiency
  • Understand how PPi levels and other markers or outcomes can change
  • Gain insights to help diagnose and treat ENPP1 deficiency
Participation in this study could help scientists better understand the disease and inform possible future treatment options.
Participants must be:
  • Diagnosed with ENPP1 deficiency (all age groups) or ABCC6 deficiency (infantile onset) through genetic testing, clinical presentation, radiologic, or biochemical testing
  • Able to provide written consent by themselves or through a legal caregiver before research
  • Have a PPi level at screening that meets the requirement
  • Willingness to provide relevant medical records and complete all aspects of the study
If enrolled, participants will complete a number of tests and visits throughout the study. These tests and visits may be time-consuming and/or require assistance from a caregiver. A researcher will thoroughly explain all requirements before enrollment.
If you have a confirmed ENPP1 (all age groups) or ABCC6 (infantile onset) diagnosis, please see additional information about study enrollment. Otherwise, keep reading to see how you can get tested for ENPP1 or ABCC6 deficiency.

The Clinical Trial for ENPP1 Deficiency

The clinical trial for ENPP1 deficiency will determine if a new medication, INZ-701, is suitable to treat those affected. Participants will be split into 3 groups. Each group will receive a different dose of INZ-701. Every 4 weeks, the dose given will increase if it is deemed safe to do so. INZ-701 is a subcutaneous injection (under the skin). Researchers will monitor participants on increasing doses of INZ-701 to:
  • Understand the safety of the medication
  • Study how the medication is processed throughout the body
  • Study changes in PPi and other markers
The estimated timing of participation is 7 weeks. Results from this study will help scientists further develop INZ-701 to treat ENPP1 deficiency.
Participants must be:
  • Male or female, 18-65 years old
  • Diagnosed with ARHR2 by a doctor with a confirmation of the ENPP1 gene
  • Able to provide written consent by themselves or through a legal caregiver before research
  • Able to discontinue the use of oral PPi from at least 14 days before and throughout treatment, if applicable
  • Able to discontinue use of bisphosphonates for 6 months prior to study start, if applicable
Women of child-bearing potential (and their male partner) must:
  • Have a negative pregnancy test at screening and during the study
  • Agree to use 2 forms of birth control from the start through 25 days after treatment
  • Agree to not donate ova from the period from the start through 25 days after treatment
Males who are sexually active must agree to:
  • Use condoms from the period from the start through 25 days after treatment
  • Not donate sperm from the period from the start through 25 days after treatment
If enrolled, participants will complete a number of tests and visits throughout the study. The tests and visits may be time-consuming and/or require assistance from a caregiver. A researcher will thoroughly explain all requirements before enrollment.
If you have a confirmed ENPP1 diagnosis and meet the criteria described, please see additional information about study enrollment. Otherwise, keep reading to see how you can get tested for ENPP1 deficiency.
Additional clinical trial information is coming soon.
Please visit the website often for an update.

The Genetic Testing Process

Consider getting tested for ENPP1 deficiency if you’ve experienced the symptoms described or have been diagnosed with GACI and/or ARHR2

Individuals who meet the eligibility criteria for the testing program can receive a no-cost, third-party genetic test to determine if they have the condition or are a carrier for ENPP1 deficiency. Those with confirmed ENPP1 status may be eligible to participate in studies to help researchers better understand and treat the condition, including the ENPP1 deficiency Prospective Observational Study previously mentioned.
Your healthcare provider (HCP) will determine if you meet eligibility criteria for a no-cost genetic test through this program.

Your HCP will order your test by following the instructions.

The genetic test will be processed at a genetic laboratory; the results will be sent to your HCP in 2-3 weeks (on average), who will discuss the results with you.
Your HCP can contact PreventionGenetics at 1‑715‑387‑0484 and/or email clinicaldnatesting@preventiongenetics.com or visit this website.

For more information, including FAQs: 

  • ABCC6, ATP binding cassette transporter protein subfamily C member 6; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1.

References

  1. Ferreira C, Ziegler S, Gahl WA. Generalized arterial calcification of infancy. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2014.
  2. Kalal IG, Seetha D, Panda A, Nitschke Y, Rutsch F. Molecular diagnosis of generalized arterial calcification of infancy (GACI). J Cardiovasc Dis Res. 2012;3(2):150-154.
  3. Data on file. Inozyme Pharma.
  4. Nitschke Y, Baujat G, Botschen U, et al. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012;90(1):25-39.
  5. Nitschke Y, Rutsch F. Generalized arterial calcification of infancy and pseudoxanthoma elasticum: two sides of the same coin. Front Genet. 2012;3:302.