THE ENPP1 DEFICIENCY PROSPECTIVE OBSERVATIONAL STUDY
Now enrolling patients with ENPP1 Deficiency (GACI or ARHR2). With your participation, healthcare providers can better understand how this disease presents and progresses over time to better inform possible future treatment options.

About ENPP1 deficiency

ENPP1 Deficiency is a rare and life-threatening genetic disorder caused by mutations in the ENPP1 gene1-3

ENPP1 Deficiency leads to a low amount of pyrophosphate (PPiA substance made by the body to control mineral buildup in soft tissues)4 This causes a disease that could affect the entire body

The time of onset and symptoms for ENPP1 Deficiency vary widely5

0-12 months
Adult
Early symptoms5-7
  • Neointimal hyperplasiaThickening 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 adulthood5-7
  • Neointimal hyperplasiaThickening 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, 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 hyperplasiaThickening 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
These 2 conditions are now known as ENPP1 Deficiency.
People with ENPP1 Deficiency have a high risk of death early in life. Those who survive face many health issues.5 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 create an effective treatment for ENPP1 Deficiency.

Participants must be:
  • Diagnosed with ENPP1 Deficiency (all age groups) or ABCC6 Deficiency (infants only) 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 (infants only) and would like to enroll in the study, please find a study site here. Otherwise, keep reading to see how you can get tested for ENPP1 or ABCC6 Deficiency.

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: 

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. Ferreira CR, Ziegler SG, Gupta A, Groden C, Hsu KS, Gahl WA. Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification. Am J Med Genet A. 2016;170a(5):1308-1311.
  3. Rutsch F, Schauerte P, Kalhoff H, Petrarulo M, August C, Diekmann L. Low levels of urinary inorganic pyrophosphate indicating systemic pyrophosphate deficiency in a boy with idiopathic infantile arterial calcification. Acta Paediatr. 2000;89(10):1265-1269.
  4. 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.
  5. Rutsch F, Ferreira C. Natural History Study of GACI/ARHR2. 2020.
  6. Oheim R, Zimmerman K, Maulding ND, et al. Human heterozygous ENPP1 deficiency is associated with early onset osteoporosis, a phenotype recapitulated in a mouse model of ENPP1 deficiency. J Bone Miner Res. 2020;35(3):528-539.
  7. Lorenz-Depiereux B, Schnabel D, Tiosano D, Hausler G, Strom TM. Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet. 2010;86(2):267-272.
  8. 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.
  9. Nitschke Y, Rutsch F. Generalized arterial calcification of infancy and pseudoxanthoma elasticum: two sides of the same coin. Front Genet. 2012;3:302.