DEVELOPMENT OF A CLINICAL SEVERITY SCORE FOR MULTIPLE ACYL-COA DEHYDROGENASE DEFICIENCY

Willemijn J. van Rijt, BSca, Panagiotis Giannopoulos, BSca and Terry G.J. Derks, MD PhDa

Affiliations: aSection of Metabolic Diseases, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, Groningen, the Netherlands.

Address correspondence to: Terry G. J. Derks, MD, PhD. E-mail: t.g.j.derks@umcg.nl. Phone: +31 (0)50 3614147.

Classically, multiple acyl-CoA dehydrogenase deficiency (MADD; glutaric aciduria type II) patients are phenotypically divided into three types. However, individual phenotypes and treatment response can vary extremely. To improve assessment of disease severity and to facilitate patient monitoring, we propose to develop an MADD-clinical severity score (CSS) at INFORM 2017.

The MADD-CSS will be designed according to a three-step method: 1) a systematic literature review and meta- analysis to identify disease symptoms and domains; 2) prioritization of disease symptoms and domains by clinical experts; 3) assembly of the MADD-CSS according to the previous steps.

Preliminary data of step 1 identified the following disease domains in 427 published patients (57 neonatal- onset, 369 later-onset and 1 unreported onset-age): CARDIAC (34/427;8.0%), CENTRAL NERVOUS SYSTEM (14/427;3.3%), PERIPHERAL NERVOUS SYSTEM (32/427;7.5%), RESPIRATORY SYSTEM (66/427;15.5%), LIVER (139/427;32.6%) and MUSCLE (372/427;87.1%).

We propose to introduce step 2 at INFORM 2017 and subsequently develop the score. The MADD-CSS can be used for a detailed patient classification and standardized assessment of disease activity and treatment efficacy, to support decision-making.