Infantile form of sialic acid storage disorder: Clinical, ultrastructural, and biochemical studies in two siblings

Abstract

We describe two sibs with coarse facies, hepatosplenomegaly, prominent psychomotor retardation and unexpectedly fair complexion. Ultrastructural studies of conjunctival, skin, bone marrow and liver biopsies from these individuals showed generalized lysosomal storage of polysaccharide-like material, i.e., membrane bound inclusions containing sparse, fibrillo-granular material. Biochemical analyses of urine and cultured fibroblasts from these patients revealed increased levels of free (unbound) sialic acid. The ultrastructural and biochemical findings in these sibs are similar to those previously found in Salla disease, however, the clinical course is much more severe. It is concluded that these children represent a new pathogenetic entity whose basic defect is still to be defined.

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

“…The skin biopsy pointed to a lysosomal storage disease, speciWcally one involving the storage of small molecules like sialic acid or an oligosaccharide [20]. The morphological Wndings in our patient were identical to those observed in skin and in conjunctiva of sialic acid storage disease patients [6,21]. However, a skin biopsy does not always show abnormal Wndings in lysosomal storage diseases, including those involving free sialic acid [18].…”

Infantile Sialic Acid Storage Disease: The Fate of Biosynthetically Labeled N-Acetyl-(3H)-Neuraminic Acid in Cultured Human Fibroblasts

“…These findings might be explained by an intralysosomal trapping of free eH)-NANA as previously suggested (2,6). In order to establish a difference in the subcellular distribution, the latency of free intracellular eH)-NANA after exposure to digitonin was investigated (Fig.…”

Studies on the defect underlying the lysosomal storage of sialic acid in Salla disease. Lysosomal accumulation of sialic acid formed from N-acetyl-mannosamine or derived from low density lipoprotein in cultured mutant fibroblasts.

“…The third type of abnormality includes Salla disease and the clinically more severe generalized sialic acid storage disease (6)(7)(8)(9)(10). This latter disorder may represent a more extensive biochemical defect similar to that of Salla disease.…”

“…A disorder resembling Salla disease, generalized N-acetylneuraminic acid storage disease, with analogous abnormalities in lysosomal sialic acid storage and urinary excretion but a more severe clinical course, has also been described (6)(7)(8)(9)(10). In this condition cellular glycoconjugate composition is normal, and defects of certain key enzymes of sialic acid metabolism have been ruled out.…”