Matt Winton, PhD, Senior Vice President and Chief Operating Officer of Inozyme Pharma, discusses results from an analysis characterizing disease severity and progression in patients with ENPP1 deficiency.
ENPP1 deficiency is a rare metabolic disease caused by mutations in the ENPP1 enzyme, responsible for the cleavage of ectonucleotides that prevent mineralization. In ENPP1 deficiency, calcium phosphate precipitates throughout the body, accumulating in the wrong places such as blood vessels, skin, eyes, joints, and tendons. This is due to low levels of pyrophosphate and ATP production.
Insufficient pyrophosphate can lead to skeletal abnormalities such as rickets and soft bone. Patients with ENPP1 deficiency also commonly experience walking and mobility issues, pain, inflammation, and bones that fracture easily. Adults may also experience hearing loss, arterial calcification, and cardiac and/or neurological involvement. Approximately half of infants with ENPP1 deficiency die within six months of birth. There are no approved therapies for ENPP1 deficiency.
Disease Severity and Progression
Recently, the paper “Phenotypic characterization of ENPP1 deficiency: generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2” was published in JBMR Plus, characterizing the severity and progression of the disease. Results from the analysis revealed that ENPP1 deficiency frequently manifests as generalized arterial calcification of infancy (GACI) or autosomal recessive hypophosphatemic rickets type 2 (ARHR2).
Of the 84 individuals with ENPP1 deficiency analyzed, 51 had a diagnosis of GACI, with only 19 of those surviving passed infancy. Additionally, 22 individuals were diagnosed with GACI that progressed to ARHR2, and 11 presented initially with ARHR2. Prenatal findings were identified in 60% of patients with a history of GACI and a GACI diagnosis was usually associated with early-onset arterial calcification, respiratory distress, heart failure, and hypertension.
Additional results from the analysis included that by age 55, over 95% of patients with ENPP1 deficiency will have experienced cardiovascular, musculoskeletal, and other organ complications. 60% of patients had arterial or aortic calcification within the first three months of life, identifying an onset of complications predominately in infancy. Cardiovascular complications were also evident in 64% of patients diagnosed with ARHR2. Finally, by age 10, about 70% of patients developed serious musculoskeletal complications, primarily rickets that greatly impaired quality of life. Additional complications in ARHR2 include hearing impairment and ongoing risk of cardiovascular complications.
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To learn more about ENPP1 deficiency and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/
