GENERALIZED N-ACETYLNEURAMINIC STORAGE WITH SIALURIA

Abstract

This case has remained unique (Fontaine, et al, Helv. Paed. Acta:23, Suppl. 17, 1968). The patient presented with mental retardation, seizures, mildly dysmorphic features, and sialuria, reaching several grams per day. The biochemical defect has not been identified. We studied biopsies from liver, kidney and skin. Hematoside level was normal in all these specimens as well as in erythrocytes. No abnormal ganglioside was detected. Significant increase of free N-acetylneuraminic acid was observed in liver, kidney and cultured skin fibroblasts. The ultrastructure of skin fibroblasts revealed scarce inclusions containing lamellar tubular cores, but no mitochondrial abnormalities such as were previously found in the liver. Skin fibroblasts were submitted to a loading test by incubation in a medium containing from 100 to 400 μg neuraminic acid per ml. This caused an increase in membrane-bound inclusions. When incubated with 14C-mannosamine, the precursor was normally incorporated into hematoside and glycoproteins. This suggested that these cells were capable of synthesizing CMP-neuraminic acid. A deficiency of neuraminic aldolase could not be disproven owing to an insufficient amount of available tissue. (Supported in part by PHS Grant HD-04612.)