Huizing et al. Page 27 Table 1: 1 2 3 A Summary of Main Features of FSASD, Sialuria, and NPL-deficiency uthor Man Disease Form Urine Free Neu5Ac4 Age at onset Main Clinical Findings Number of Cases (fold increase) Moderate global developmental delay uscr Mild cognitive dysfunction Speech delay Muscle hypotonia, cerebellar ataxia ipt Mild FSASD ~10-fold 6–12 mo Spasticity ~ 160 Salla disease Seizures or epilepsy Mostly hypomyelination on brain MRI Motor disability, able to walk With or without coarse facial features Near normal life span Moderate/severe global developmental delay Growth delay or failure to thrive Severe muscle hypotonia Cerebellar ataxia, spasticity A Intermediate FSASD ~15–100-fold 1–6 mo Seizures, epilepsy ~ 25 uthor Man Intermediate severe SASD Hypomyelination on brain MRI Mild coarse facial features No or mild organomegaly Nephrosis Shortened life span Intrauterine hydrops, neonatal ascites uscr Failure to thrive Severe global developmental delay Severe FSASD Coarse facial features ipt ISSD >100-fold intrauterine Dysmorphic features ~ 15 Hepatosplenomegaly, cardiomegaly Nephrosis Early death (age < 2 years) Coarse facial features Sialuria 100–1000-fold infancy Organomegaly 11 Developmental delay NPL deficiency 10-fold childhood Progressive cardiac myopathy 2 A Mild skeletal myopathy uthor Man Abbreviations: ISSD: infantile sialic acid storage disorder; FSASD: free sialic acid storage disorder; mo: months; NPL: N-acetylneuraminate pyruvate lyase; SASD: sialic acid storage disorder 1Based on [9–11, 65, 126, 127] uscr 2Based on [33, 41, 42] 3 ipt 4Based on [38] Range of free Neu5Ac in normal controls: 7–194 nmol/mg creatinine [127] 5Additional sporadic clinical features of FSASD include ascites, athetosis, cardiomegaly, corneal clouding, hoarse voice, hypopigmentation, nephropathy, nystagmus, optic atrophy, ptosis, recurrent airway infections and short stature [11, 65] A uthor Man uscr ipt Neurosci Lett. Author manuscript; available in PMC 2021 June 11.