Neuraminidase deficiency

There are other lysosomal disorders in addition to those shown in Figure 9.20 and Table 9.1. For instance, several types of fucosidoses exist, which affect such structures as glycoproteins and blood group substances. Sialidoses also exist. However, lysosomal fucosidase and sialidase (neuraminidase) deficiencies do not affect the degradation of gangliosides. 

The last example of a modification of RIS as a result of a mutation is that of liver neuraminidase in the SM/J mouse (Yan et al., unpublished work). The SM/J mouse is a mutant with a severe 4-methylumbelliferyl-a-D-V-acetylneuraminate neuraminidase deficiency in the liver (Potier et al., 1979). The residual neuraminidase activity in SM/J mouse liver is due to a thermostable component that differs in isoelectric point and RIS... 

Neuraminidase Deficiency. A simple defect in lysosomal neuraminidase has only recently come to light (Lowden and O Brien, 1979 Kuriyama etal, 1979). Patients with this storage disease put out sialo-oligosaccharides in their urine. Fibroblasts from the patient of Kuriyama et al, (1979) showed an extreme deficiency in neuraminidase activity towards a2,3-sialyl lactose, a2,6-sialyl lactose and fetuin. Hence more than one enzyme might be involved. 

Mucolipidosis I has been shown to be associated with the excretion of O- and A -glycopeptides, a finding which is in agreement with a report on a neuraminidase deficiency for this disease. 360 MHz H N.m.r. spectra have been recorded for ten urinary sialyl-oligosaccharides isolated from patients with mucolipidosis I and II, 3 -sialyl-lactose has been isolated from normal... 

The pinocytosis by fibroblasts of j8-D-2-acetamido-2-deoxyhexosidase excreted by cultural skin fibroblasts from a patient with I-cell disease was not enhanced by neuraminidase treatment of the enzyme. The uptake of the normal plasma enzyme was minimal and this was not appreciably enhanced by neuraminidase treatment. In contrast, normal seminal fluid j3-D-2-acetamido-deoxyhexosidase was readily pinocytosed regardless of neuraminidase treatment. Thus it was concluded that a neuraminidase deficiency in I-cell disease may not be directly responsible for excessive extracellular enzyme. 

Galactosialidosis (late infantile) (Secondary galacto sidase and a-neuraminidase deficiencies) ... 

Gmi ganghosidosis, G j ganghosidosis, siahc acid storage disorder, siahdase/neuraminidase deficiency, galactosialidosis, I-cell disease, fucosidosis, and Pompe and Gaucher diseases. 

Tong, H.H., James, M., Grants, I., Liu, X., Shi, G. and DeMaria, T.F., Comparison of structural changes of cell surface carbohydrates in the eustachian tube epithelium of chinchillas infected with a Streptococcus pneumoniae neuraminidase-deficient mutant or its isogenic parent strain. Microb. Pathog., 31, 309-317 (2001). 

Messer 1979). This gene dosage effect indicated that the neuraminidase deficiency was primary. A similar neuraminidase deficiency was demonstrated in an infant with clinical symptoms suggestive of mucolipidosis I (Kelly and Graetz 1977) and in patients with nephrosialidosis , a combination of the symptoms of mucolipidosis I with renal disease (Maroteaux etal. 1978 a). In these patients, there was likewise a massive excretion of sialyloligosaccharides in the urine. 

In addition to these two types of sialidosis, there are patients with a combined defect of neuraminidase and p-galactosidase (Wenger etal. 1978, Andria etal. 1978, OK.ADAetal. 1979), possibly caused by a common defect in the biosynthetic processing of the two enzymes (Hoogeveen etal. 1980). A neuraminidase deficiency has also been observed in patients with mucolipidosis II (I-cell disease) and mucolipidosis III (Strecker etal. 1976, Thomas etal. 1976). In these disorders, however, the neuraminidase deficiency is but one of many lysosomal hydrolase deficiencies, presumably due to a defect in the proper compart-mentalization of these enzymes (Neufeld 1974). 

A neuraminidase deficiency has also been observed in a strain of mice (designated SM/J) by Potier etal. (1979a) using the synthetic substrate 4-methylumbelliferyl-a-D-N-acetylneuraminic acid. This deficiency is confined... 

As neuraminidase activity is readily detectable in amniotic cells, a prenatal diagnosis should be possible in a fetus at risk for sialidosis. Indeed, prenatal diagnosis has been performed in a pregnancy at risk for combined p-galactosidase/neuraminidase deficiency, and the diagnosis of an affected fetus was confirmed by assays of neuraminidase and p-galactosidase in tissues from the aborted fetus Kleuer etal. 1979). 

Sialidosis with isolated neuraminidase deficiency occurs in at least two clinical phenotypes a severe form with HuRLER-like appearance, myoclonus, cherry-red spots of the retina, mental retardation and, sometimes, with renal disease, and a mild form with or without mental retardation, with myoclonus and with cherry-red spots. Quite likely, the two forms originate from allelic mutations of the same neuraminidase gene, giving rise to enzyme deficiency states of varying degrees. 

The combined p-galactosidase/neuraminidase deficiency, on the other hand, presents a clinical picture which seems intermediate in severity between the mild and severe forms of isolated neuraminidase deficiency. Whereas it is not yet clear whether the neuraminidase deficiency in this disorder is secondary to an unknown processing defect, a defect in such a mechanism has been shown to be responsible for the deficiency of numerous lysosomal hydrolases, including neuraminidase, in patients with mucolipidoses II and III. 

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