Huizing et al. Page 3 multidisciplinary collaborative efforts involving the National Institutes of Health (NIH), A uthor Man academic clinical scientists, and patient advocacy groups have successfully overcome the scientific, clinical and financial challenges facing the development of new drug treatments for similar rare diseases [20, 22]. Encouraged by these successes, we initiated a collaborative FSASD consortium, including NIH-based and worldwide academic scientists with clinical uscr and basic FSASD research expertise, and the Salla Treatment and Research (S.T.A.R.) Foundation patient advocacy group (https://www.sallaresearch.org/). This consortium will ipt create and study preclinical cell and mouse models, perform basic/translational research, initiate a natural history study to aid in the identification of biomarkers and treatment endpoints, and investigate drug candidates. By generating these data and raising awareness of FSASDs, we hope to incentivize industry to further develop, obtain approval, and commercialize FSASD treatments. A This review addresses the current status, progress, pending requirements and opportunities to uthor Man advance drug development efforts for this intriguing rare inborn error of sialic acid metabolism. uscr 1. FSASD Disease Nomenclature When FSASD was first described by Aula et al., 1978 it was named Salla disease after the ipt geographical region in Finnish Lapland where the first known patients resided [16]. Later, individuals outside of Finland with a much more severe clinical course were described as exhibiting infantile sialic acid storage disorder (ISSD) [23]; other reports named the disorder sialic acid storage disorder (SASD) [7, 24] or Finnish type sialuria [25] to distinguish it from the non-lysosomal form of excessive sialic acid production, French type sialuria (MIM#269921) [26, 27]. The term Salla disease is now used in the literature not only for A uthor Man FSASD cases with the Finnish founder variant in SLC17A5, but also for any mild FSASD cases, independent of the mutation or region of origin. The multiple historic names for this allelic disorder, all caused by defects in the gene uscr SLC17A5, continue to be used in the literature and disease databases. This becomes increasingly confusing for clinicians, patients, researchers, genetic diagnostic laboratories ipt and disease databases and, ultimately, the pharmaceutical rare disease industry. Therefore, we propose to consistently name the disorder ‘Free Sialic Acid Storage Disorder’ (FSASD), referring to the entire spectrum of disease severity and replacing all previous disease definitions. With FSASD referring to the entire spectrum of disorders associated with SLC17A5 deficiency, improvements will follow in worldwide disease awareness, diagnosis, estimations of disease prevalence and, ultimately, support for a path to therapy. A uthor Man 2. Sialic Acid Metabolism Sialic acids are a diverse family of negatively charged sugars and occupy terminal positions of oligosaccharide chains of most glycans (glycoproteins and gangliosides), on which they uscr mediate a variety of biological functions and play essential roles in disease processes [28, ipt 29]. The most abundant mammalian sialic acid and the precursor of most other sialic acids is N-acetylneuraminic acid (Neu5Ac), generally referred to as sialic acid [29, 30]. Free sialic Neurosci Lett. Author manuscript; available in PMC 2021 June 11.