Quantitative definition of the natural history of free sialic acid storage disease (SASD, OMIM 604369), an orphan disorder due to the deficiency of the proton-driven carrier SLC17A5.
Analysis of published cases with SASD (N = 116) respecting STROBE criteria. Main outcome parameters: survival and diagnostic delay. Phenotype, phenotype–biomarker associations, and geographical patient distribution were explored.
Median age at disease onset was 0.17 years. Median age at diagnosis was 3 years with a median diagnostic delay of 2.5 years. Median survival was 11 years. The biochemical phenotype clearly predicted the disease course: patients with a urinary free sialic acid excretion below 6.37-fold or an intracellular free sialic acid storage in fibroblasts below 7.37-fold of the mean of normal survived longer than patients with biochemical values above these thresholds. Cluster analysis of disease features suggested a continuous phenotypic spectrum. Patient distribution was panethnic.
Combination of neurologic symptoms, visceromegaly, and dysmorphic features and/or nonimmune hydrops fetalis should prompt specific tests for SASD, reducing diagnostic delay. The present quantitative data inform clinical studies and may stimulate and accelerate development of specific therapies. Biomarker–phenotype association is particularly important for both counseling parents and study design.
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M.Z. received support from the Physician-Scientist Program at Ruprecht-Karls-University Heidelberg Faculty of Medicine.
The authors declare no conflicts of interest.
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Zielonka, M., Garbade, S.F., Kölker, S. et al. A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease—an ultra-orphan multisystemic lysosomal storage disorder. Genet Med 21, 347–352 (2019). https://doi.org/10.1038/s41436-018-0051-3
- Sialic acid storage disease
- Natural history
- Drug development
- Orphan disease
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