Inherited metabolic disorders are multi-organ diseases and highly variable with respect to age of onset and clinical severity. A large proportion of these patients are affected by significant skeletal alteration including early-onset low Bone Mineral Density (BMD). Nevertheless, systematic diagnostic work-up focusing on low BMD is not yet standard of care. The identification and characterization of pediatric patients with low BMD in inherited metabolic disorders will be integrated into routine clinical follow-up as a new standard of care. The skeletal phenotype of patients will be characterized in detail with a special focus on the phenotypic severity, the underlying gene defects and effects of treatment. Furthermore, in a newly established patient registry for low BMD disorders in pediatric patients (BonePedia) data on skeletal disease manifestations and osteological assessments will be collected and analyzed. These data might serve as a basis for the development of diagnostic and treatment recommendations which are highly relevant to clinicians and patients. A typical metabolic disorder affecting the skeletal system is mucolipidosis type II (ML II). So far, there is no treatment available for patients with this condition. Therefore, a precision medicine strategy using RNA editing in a novel mouse model for MLII will be developed. All work packages of project 2 will be done in close cooperation with other partners within the ProBone network.

Department of Pediatrics