GACI Global, Argyle, Texas, United States of America.
Inozyme Pharma Inc, Boston, Massachusetts, United States of America.
PLoS One. 2022 Jul 27;17(7):e0270632. doi: 10.1371/journal.pone.0270632. eCollection 2022.
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.
核苷酸焦磷酸酶/磷酸二酯酶家族成员 1（ENPP1）和 ATP 结合盒亚家族 C 成员 6（ABCC6）蛋白在抑制异位钙化和动脉狭窄方面发挥着重要作用。ENPP1 缺乏症或婴儿期起病的 ABCC6 缺乏症患者常表现为病理性钙化、血管狭窄、多器官功能障碍和高婴儿死亡率。其异质性表现和进展有充分的记录。我们的目标是从患者/照顾者的角度描述这些疾病如何导致发病和生活质量下降。通过机构审查委员会批准的问卷，通过电话对患者/照顾者进行访谈。通过经过验证的工具收集患者报告的结果。31 名照顾者和 7 名患者参与：婴儿期起病的 ABCC6 缺乏症，n = 6（婴儿/儿童）；ENPP1 缺乏症，n = 32（13 名婴儿，12 名儿童，7 名成人）。年龄<8 岁和 8-18 岁的 ENPP1 和 ABCC6 缺乏症儿童报告学习成绩不佳（分别为 0.69 和 0.72 的效应大小）和身体健康状况不佳（分别为 0.88 和 1）。在整个 ENPP1 队列中，72%（23/32）报告有骨骼/关节疼痛和/或活动能力/疲劳问题。7 名 ENPP1 缺乏症成人中有 3 名报告中度至重度疼痛（>4），这是由简明疼痛量表（BPI）测量的，尽管服用了止痛药，但疼痛仍会干扰日常活动。ABCC6/ENPP1 缺乏症婴儿的照顾者报告的最大负担包括与心脏相关的问题和住院治疗。治疗/药物和听力损失是儿科 ENPP1 缺乏症患者照顾者/家庭报告的最高负担，而成年人则报告骨骼/关节疼痛和活动能力障碍是最大负担。ENPP1 缺乏症或婴儿期起病的 ABCC6 缺乏症患者会终生患病，给患者/照顾者带来巨大的身体和情感负担。
