24 Development of a suspicion index tool to aid diagnosis of ASMD disease

The diagnosis of acid sphinogomyelinase deficiency (ASMD, Niemann Pick Type A, A/B, B) is frequently delayed by years, due to the highly heterogeneous and often unspecific clinical features. The involvement of different organs, the musculoskeletal system and the central nervous system (especially in infantile neurovisceral/chronic neurovisceral forms of ASMD) represent a diagnostic challenge. Therefore, we aim to develop an innovative suspicion index tool (SIT) for health care professionals to enable an early and accurate diagnosis of ASMD. Our developed SIT is based on validated tools with literature research for type specific clinical features and differential diagnosis as well as a multi-center chart review with international ASMD centers in Europe and America. ASMD symptoms were categorized into skeletal, vis-ceral and neurologic domains. The finally developed scoring system results from the predic-tion of single symptoms and symptom combinations, as well as ASMD family history via lo-gistic regression. So far, 160 ASMD patients, non-cases and controls (M.Gaucher, M.Wolman, NPD-C) from literature and 48 further ASMD patients by expert chart review have been analyzed (ongoing). Key clinical signs were defined as those observed in >10% of ASMD cases. Symptoms occur-ring in more than one category (skeletal, visceral, neurological) as well as family relationships were strong indicators of ASMD. Visceral symptoms were highly suggestive, including sple-nomegaly, hepatomegaly, and mixed dyslipidemia with reduced HDL-C levels (last solely ASMD type B). So far, our strategy has been very feasible. After the expert chart review is finished, we will finalize the scoring system and implement it as mobile device app for evidence-based clinical support.