A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease

• Verfasst von: Zielonka, Matthias [VerfasserIn]
• Verfasst von: Garbade, Sven [VerfasserIn]
• Verfasst von: Kölker, Stefan [VerfasserIn]
• Verfasst von: Hoffmann, Georg Friedrich [VerfasserIn]
• Verfasst von: Ries, Markus [VerfasserIn]
• Titel: A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease
• Titelzusatz: an ultra-orphan multisystemic lysosomal storage disorder
• Verf.angabe: Matthias Zielonka MD, Sven F. Garbade PhD, Stefan Kölker MD, Georg F. Hoffmann MD & Markus Ries MD, PhD
• Jahr: 2019
• Jahr des Originals: 2018
• Umfang: 6 S.
• Fussnoten: Published: 06 June 2018 ; Gesehen am 17.04.2019
• Titel Quelle: Enthalten in: Genetics in medicine
• Ort Quelle: London, UK : Springer Nature, 1998
• Jahr Quelle: 2019
• Band/Heft Quelle: 21(2019), 2, Seite 347-352
• ISSN Quelle: 1530-0366
• DOI: doi:10.1038/s41436-018-0051-3
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1663395403

Abstract

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.