Clinical spectrum of infantile free sialic acid storage disease

Infantile free sialic acid storage disease(ISSD) is a rare autosomal recessive metabolic disorder caused by a lysosomal membrane transportdefect, resulting in accumulation of free sialic acidwithin 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 asciteswith heart failure, and a case of fetal asciteswith 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 retardationare constant findings in this disorder. 2) Nephrotic syndromeoccurred in most cases (four in seven) in which renal evaluation was performed. Therefore, ISSD is an important cause of nephrosisin infants with a storage disorder phenotype. 3) Fetal/neonatal ascitesor hydrops was the mode of presentation in 13 (60%) of 21 cases. Thus, ISSD enters in the differential diagnosis of hydrops fetaliswith a storage disease phenotype. 4) Cardiomegaly was evident in nine cases. 5) Corneae were always clear, and albinoidfundi were reported in five cases. 6) Dysostosis multiplexwas not prominent. 7) Bone marrow aspirationcould 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. © 1999 Wiley-Liss, Inc.