Largest pediatric analysis to date of literature-based real-world evidence shows wide spectrum of cardiovascular, neurologic, and ocular complications
ANN ARBOR, MICH. - December 5, 2025 - FOR IMMEDIATE RELEASE
Genomenon®, Inc., a leading genomic intelligence company, announced the publication of a paper in Orphanet Journal of Rare Diseases summarizing the real-world evidence (RWE) found across the biomedical literature on the clinical and genetic findings in children with ABCC6 deficiency. The study, completed in collaboration with Inozyme Pharma (acquired by BioMarin), is the most comprehensive pediatric analysis to date and underscores the need for earlier recognition and systematic monitoring of this rare, multisystem mineralization disorder.
Key findings from the paper include the RWE on 95 children (0 to <18 years) with ABCC6 deficiency and documented clinical signs, in whom 133 unique ABCC6 variants were identified, most classified as pathogenic or likely pathogenic. The analysis revealed a high prevalence of ectopic calcification with cardiovascular, neurologic, dermatologic, and ocular complications, often emerging in early childhood, with most reported clinical events occurring before six years of age. While many patients were clinically labeled as having generalized arterial calcification of infancy type 2 (GACI2) or pseudoxanthoma elasticum (PXE), a substantial proportion showed overlapping features of both, with no simple genotype-phenotype rules to predict severity or organ involvement.
“Our findings make it clear that pediatric ABCC6 deficiency doesn’t fit into a single diagnostic label,” said Amina Kozaric, principal scientist and co-author of the paper at Genomenon. “These children may come in with stroke, seizures, hypertension, cardiac disease, skin changes, or vision problems - often in combination - and picking up that pattern early is essential if we want to change their trajectory.”
Researchers identified pediatric cases of ABCC6 deficiency through a comprehensive literature review using Genomenon’s Mastermind Genomic Intelligence platform, a database of variants with evidence cited in the medical literature. They then integrated these data with two natural history studies of patients with GACI2 and PXE, along with additional unpublished patients, and interpreted the combined dataset to clinical standards. This approach resulted in the most complete pediatric patient and variant database for ABCC6 deficiency-associated diseases to date and supports the development of clearer guidelines for assessment, genetic diagnosis, monitoring, and prognostic counseling.
“By pulling decades of scattered reports into one cohesive analysis, this work gives clinicians a clearer roadmap for recognizing ABCC6 deficiency in real-world pediatric patients,” said Kozaric. “Our hope is that it shortens the diagnostic odyssey and supports more proactive, coordinated care for these families.”
Co-authors of the paper, “Pediatric ABCC6 deficiency: a genotypic and phenotypic analysis,” include Marta Bertamino, David J. Goldberg, M. Zulf Mughal, Lisa Pabst, Yaping Joyce Liao, Lisa R. Sun, Jane Beckwell, Amina Kozaric, Ruth du Moulin, Katie Swanner, Carlos R. Ferreira, and Shira G. Ziegler.
Data analysis was conducted by Genomenon, Inc. Medical writing and editorial support were funded by Inozyme Pharma, Inc.
Genomenon® is a genomic intelligence company transforming patient care by uncovering the genomic drivers of genetic disease and cancer. By combining the power of AI built on a comprehensive genomic dataset with deep scientific expertise, Genomenon delivers structured, actionable insights that support advanced patient diagnosis and accelerate precision medicine development. Its integrated software, data, and services solutions empower biopharma and clinical partners worldwide.
