A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease-an ultra-orphan multisystemic lysosomal storage disorder

Genet Med. 2019 Feb;21(2):347-352. doi: 10.1038/s41436-018-0051-3. Epub 2018 Jun 6.


Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Drug development; Natural history; Orphan disease; SLC17A5; Sialic acid storage disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Biomarkers
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cross-Sectional Studies
  • Delayed Diagnosis
  • Female
  • Humans
  • Infant
  • Male
  • N-Acetylneuraminic Acid / urine
  • Phenotype
  • Pregnancy
  • Prenatal Diagnosis
  • Sialic Acid Storage Disease* / diagnosis
  • Sialic Acid Storage Disease* / epidemiology
  • Sialic Acid Storage Disease* / pathology
  • Survival Analysis


  • Biomarkers
  • N-Acetylneuraminic Acid

Supplementary concepts

  • Free sialic acid storage disease