Lifelong impact of ENPP1 Deficiency and the early onset form of ABCC6 Deficiency from patient or caregiver perspective

PLoS One. 2022 Jul 27;17(7):e0270632. doi: 10.1371/journal.pone.0270632. eCollection 2022.

Abstract

The ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) and ATP-binding cassette subfamily C member 6 (ABCC6) proteins play a prominent role in inhibiting ectopic calcification and arterial stenosis. Patients with ENPP1 Deficiency or infant onset ABCC6 Deficiency often present with pathological calcification, narrowed blood vessels, multiorgan dysfunction and high infant mortality. The heterogenous presentation and progression is well documented. Our objective was to characterize how these morbidities lead to burden of illness and poor quality of life across ages from the patient/caregiver perspective. Patients/caregivers were interviewed via phone using Institutional Review Board-approved questionnaires. Patient-reported outcomes were collected via validated instruments. Thirty-one caregivers and 7 patients participated: infant onset ABCC6 Deficiency, n = 6 (infants/children); ENPP1 Deficiency, n = 32 (13 infants, 12 children, 7 adults). ENPP1 and ABCC6-deficient children aged <8 years and aged 8-18 years reported poor school functioning (0.69 vs 0.72 effect size, respectively) and poor physical health (0.88 vs 1, respectively). In the total ENPP1 cohort, 72% (23/32) reported bone/joint pain and/or mobility/fatigue issues. Three of seven ENPP1-deficient adults reported moderate to severe pain (>4), as measured by the Brief Pain Inventory (BPI), that interfered with daily activities despite pain medication. Top reported burdens for caregivers of infants with ABCC6/ENPP1 Deficiencies included heart-related issues and hospitalizations. Treatment/medications, and hearing loss were the highest burdens reported by caregivers/families of the pediatric ENPP1 Deficiency cohort, whereas adults reported bone/joint pain and mobility impairment as the greatest burdens. Individuals with ENPP1 Deficiency or infant onset ABCC6 Deficiency experience lifelong morbidity causing substantial physical and emotional burden to patients/caregivers.

MeSH terms

  • Adolescent
  • Adult
  • Arthralgia
  • Caregivers*
  • Child
  • Humans
  • Infant
  • Multidrug Resistance-Associated Proteins* / deficiency
  • Multidrug Resistance-Associated Proteins* / genetics
  • Pain
  • Phosphoric Diester Hydrolases* / deficiency
  • Phosphoric Diester Hydrolases* / genetics
  • Pyrophosphatases* / deficiency
  • Pyrophosphatases* / genetics
  • Quality of Life*

Substances

  • ABCC6 protein, human
  • Multidrug Resistance-Associated Proteins
  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases

Grants and funding

The study was funded by Inozyme Pharma, Inc (www.inozymepharma.com). The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this manuscript. GHK, PH, BML, and CAN were employees of Inozyme Pharma, Inc at the time the study was completed. The authors acknowledge the editorial assistance of Leleesha Samaraweera, PhD of PRECISIONscientia, Inc in Yardley, Pennsylvania, which was supported financially by Inozyme Pharma, Inc in compliance with international Good Publication Practice guidelines. The study design and questions were developed as a collaboration between Engage Health, Inc, GACI Global and researchers from Inozyme Pharma, Inc. Representatives from Engage Health, Inc conducted the patient interviews. Statistical analysis was performed by Engage Health, Inc and Inozyme Pharma, Inc based on a pre-determined statistical analysis plan. The funders had no role in the decision to publish or preparation of the manuscript.