Clinical spectrum of infantile free sialic acid storage disease

Abstract

Infantile free sialic acid storage disease (ISSD) is a rare autosomal recessive metabolic disorder caused by a lysosomal membrane transport defect, resulting in accumulation of free sialic acid within lysosomes. Only a few cases have been described. We report on three new cases of ISSD with different modes of presentation: an infant with nephrotic syndrome, a case of fetal and neonatal ascites with heart failure, and a case of fetal ascites with esophageal atresia type III. From these patients and a review of the literature (27 cases total) we draw the following conclusions. 1) ''Coarse facies,'' fair complexion, hepatosplenomegaly, and severe psychomotor retardation are constant findings in this disorder. 2) Nephrotic syndrome occurred in most cases (four in seven) in which renal evaluation was performed. Therefore, ISSD is an important cause of nephrosis in infants with a storage disorder phenotype. 3) Fetal/neonatal ascites or hydrops was the mode of presentation in 13 (60%) of 21 cases. Thus, ISSD enters in the differential diagnosis of hydrops fetalis with a storage disease phenotype. 4) Cardiomegaly was evident in nine cases. 5) Corneae were always clear, and albinoid fundi were reported in five cases. 6) Dysostosis multiplex was not prominent. 7) Bone marrow aspiration could be negative. 8) Death ensued in early infancy with a mean age of 13.1 months. All reported deaths were caused by respiratory infections. Am. J. Med. Genet. 82:385-391, 1999.

Infantile Sialic Acid Storage Disease: Two Unrelated Inuit Cases Homozygous for a Common Novel SLC17A5 Mutation

“…Determining whether this is the case will require analysis of a larger ethnic cohort and/or use of SNP-based linkage disequilibrium methods, beyond the scope of this report. The distribution of the observed storage material in our patients is similar to that reported previously (Lemyre et al 1999), and corresponds in a general sense to the expression pattern of sialin in the mouse (Yarovaya et al 2005).…”

“…We are aware of one earlier report of two children with free sialic acid storage and increased neuraminidase activity in lymphocytes, although activity was normal in fibroblasts in these same patients (Ylitalo et al 1986). In contrast, several authors have reported neuraminidase activity in ISSD patients as "normal" or "not decreased" (Baumk€ otter et al 1985;Paschke et al 1986;Pueschel et al 1988;Fois et al 1987;Nakano et al 1996;Lemyre et al 1999). Whether this apparent inconsistency represents true biological variation, differences in technique, or a chance observation due to the influence of other genetic modifiers is unclear at present.…”

“…Recently, SLC17A5 mutations have also been identified in children and adults with cerebral palsy-like chronic encephalopathy; thus, the recognized spectrum of clinical phenotypes continues to expand (Debray et al 2011;Mochel et al 2009Mochel et al , 2010. ISSD is situated at the opposite (severe) end of the SLC17A5 disease spectrum; cardinal features include profound developmental delay, failure to thrive, hepatosplenomegaly, coarse facies, hypopigmentation, and (typically) death in infancy (Lemyre et al 1999). Findings seen in a subset of cases include dysostosis multiplex, cardiomegaly, heart failure, and prematurity.…”

Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity

“…In a mild type of lysosomal free sialic acid storage, i.e., Salla disease common in Finland, newborns develop intellectual impairment gradually. In the more severe allelic variant, i.e., infantile free sialic acid storage disease (ISSD), patients generally die early in childhood or even in utero [2]. Individuals with symptoms of moderate severity are considered to have "intermediate severe Salla disease."…”

Clinical, biochemical, and cytochemical studies on a Japanese Salla disease case associated with a renal disorder

“…However, Lemyre et al (1999) showed that a nephrotic syndrome occurred in four of seven ISSD patients in whom renal evaluation was performed, and ISSD seems to be an important cause of nephrosis in infants with a storage disorder phenotype.…”