ECEESPE2025 Poster Presentations Bone and Mineral Metabolism (112 abstracts)
Quantitative evaluation of hypophosphatemic rickets due to ENPP1 deficiency
Leanne Ward 1 , David Weber 2 , Frank Rutsch 3 , Alix Bensacon 4 , Klaus Dieterich 5 , Thomas Perouse de Montclos 6 , Suma Uday 7 , Deborah Wenkert 8 , Nagwa Wilson 9 , Khaldoun Koujok 9 , Kevin Smit 10 , Stefan Jackowski 11 , Maya Scharke 11 , Robert Mensah 12 , Kurt C Gunter 12 , M. Zulf Mughal 13 & Thomas Thacher & 15
1Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada; 2Children’s Hospital of Philadelphia, Philadelphia, PA, United States; 3Muenster University Children’s Hospital, Muenster, Germany; 4Hôpital Universitaire Necker Enfants-Malades, Pediatric Endocrinology and Diabetes, Paris, France; 5Univ. Grenoble Alpes, Inserm 1209, IAB, CHU Grenoble Alpes, Grenoble, France; 6Centre Hospitalier Universitaire (CHU) de Lyon, Lyon, France; 7Birmingham Women’s and Children’s Hospital, Birmingham, United Kingdom; 8Wenkert & Young, LLC, Thousand Oaks, CA, United States; 9Children’s Hospital of Eastern Ontario, University of Ottawa, Department of Medical Imaging, Ottawa, Ontario, Canada; 10Children’s Hospital of Eastern Ontario, University of Ottawa, Department of Surgery, Division of Pediatric Orthopedics, Ottawa, Ontario, Canada; 11The Ottawa Pediatric Bone Health Research Group, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada; 12Inozyme Pharma, Boston, MA, United States; 13Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates; 14Mayo Clinic, Rochester, MN, United States; 15Mayo Clinic, Rochester, United States
JOINT571
Introduction: ENPP1 is a critical enzyme involved in the generation of pyrophosphate, an inhibitor of skeletal mineralization, and adenosine, a regulator of vascular intimal proliferation. Patients with biallelic, loss of function ENPP1 variants typically present at birth with severe arterial calcification and cardiovascular complications, a phenotype described as Generalized Arterial Calcification of Infancy Type 1 (GACI Type 1). Those who survive beyond infancy develop Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2), with deficient mineralization of the bone and growth plate leading to impaired growth and skeletal deformities.
Purpose: To describe Rickets Severity Score (RSS), height, bone age, Bone Health Index (a surrogate for bone strength), and treatments/interventions in pediatric patients with ENPP1 Deficiency under current standard of care.
Methods: Sub-group analysis of a multicenter longitudinal retrospective chart review, including patients with clinical and genetic diagnosis of ENPP1 Deficiency. In a post-hoc analysis, Bone Age and Bone Health Index were calculated using BoneXpertTM software.
Results: Fourteen patients with ENPP1 Deficiency were enrolled. Two died in infancy, and 12 were enrolled at a median age of 19. 5 years (range: 4-33). Seven patients were diagnosed with GACI, and 10 with ARHR2 at a median age of 5 years (range 0. 3 – 21), including 3 with both phenotypes. All 7 with GACI required medication (n = 6) and/or respiratory support (n = 5) in infancy; 5/12 surviving patients (42%) received at least one antihypertensive in childhood or early adulthood. Nine surviving patients (75%) required medication for rickets (vitamin D analogs n = 9; phosphate supplements n = 8), 9 had at least one orthopedic surgery (epiphysiodesis n = 7, osteotomy n = 5), and 6 wore hearing aids. All 13 patients assessed were hypophosphatemic, and 11/13 had elevated alkaline phosphatase (ALP) levels. Median Global RSS in children <13 years of age (n = 8) was 1. 75 (range 0-3). Height Z scores tended to decline over time. At final follow up, 5 patients had short stature (Z score ≤-2) including 3 patients with stature Z scores more than 3. 0 standard deviations below the mean. Mean bone age was delayed by 0. 87±1. 28 years relative to chronological age (P < 0. 01), as calculated by BoneXpert assessment of 33 hand X-rays across 9 patients. Mean Bone Health Index Z score was reduced at -1. 31±1. 33; P < 0. 001.
Conclusions: Children with ENPP1 Deficiency under current standard of care exhibit considerable and heterogenous impairments in bone health, overlapping with other forms of genetic hypophosphatemias. In addition, surviving patients may require treatments/interventions for hypertension and hearing loss.
Volume 110
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Endocrine Abstracts
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