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

Paschke, Eduard; Höfler, Gerald; Roscher, Adelbert A.

doi:10.1203/00006450-198608000-00015

Cited by 10 publications

(2 citation statements)

References 9 publications

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“…This may be explained by the assumption that accumulated free N A N A in ISSD resides in a metabolic pool that is not available for biosynthetic utilization. Furthermore, normal incorporation rates of radioactive precursors into sialoglycoconjugates have been reported (Thomas et al, 1983;Paschke et al, 1986a). Taken together, the normal response of ISSD fibroblasts to glucosamine loading clearly discriminates ISSD from sialuria and provides further evidence for unimpaired de novo synthesis of free N A N A and N A N A glycoconjugates.…”

Section: Table 1 Influence Of D-(+)-glucosamine On Intracellular Concmentioning

confidence: 86%

The effect ofd‐(+)‐glucosamine on levels of freeN‐acetylneuraminic acid and UDP‐N‐acetylhexosamines in infantile sialic acid storage disease (ISSD) fibroblasts

Paschke

Höfler

Roscher

1986

J of Inher Metab Disea

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An impairment in the regulation of N-acetylneuraminic acid (NANA) biosynthesis might potentially contribute to accumulation of free NANA in fibroblasts of patients with sialic acid storage disease (ISSD). By the use of a glucosamine loading test an increase in uridine-diphosphate-N-acetyl-hexosamines (UDP-HexNAc) but not in free NANA was found. NANA biosynthesis therefore appears to be under normal regulatory control in ISSD.

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Section: Table 1 Influence Of D-(+)-glucosamine On Intracellular Concmentioning

confidence: 86%

The effect ofd‐(+)‐glucosamine on levels of freeN‐acetylneuraminic acid and UDP‐N‐acetylhexosamines in infantile sialic acid storage disease (ISSD) fibroblasts

Paschke

Höfler

Roscher

1986

J of Inher Metab Disea

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“…Both compounds are shown to have considerable influence on glomerular function (Brenner et aI., 1978). In ISSD --a defect in a proton-driven transport system for free sialic and glucuronic acid (Mancini et al, 1989, Tietze et al, 1989) --other causes for the development of a nephrosis should be present, since all steps in the metabolism of free sialic acid, including its biosynthesis in the cytosol, its incorporation into glycoproteins and glycolipids and its liberation from these compounds in the lysosomal compartment, were shown to be normal (Hancock et al, 1983;Paschke et al 1986aPaschke et al , 1987Renlund et aI, 1983Renlund et aI, , 1986aMendla et al, 1988).…”

Section: Discussionmentioning

confidence: 97%

Storage material from urine and tissues in the nephropathic phenotype of infantile sialic acid storage disease

Paschke

Gruber

Ring

et al. 1991

J of Inher Metab Disea

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We analysed urine and tissue specimens from two nephrotic infantile sialic acid storage disease patients (nISSD) for free and bound sialic acids in comparison to non-nephrotic ISSD patients (ISSD), patients with minimal change nephrosis (nControl) and normal controls (Control). No differences in the excretion of urinary free sialic acid could be detected between ISSD and nISSD urines. Sialyloligosaccharide fractions were only slightly elevated and of apparently normal composition. Owing to glomerular dysfunction, measurable quantities of protein-bound sialic acids were present in nISSD and nControl. In nISSD tissues, free sialic acid was elevated 18-100-fold above control and 3-12-fold above Niemann-Pick A (NPA) samples. The storage of membrane-bound sialic acid was slightly increased compared to control tissues, but equal to those from NPA, thus reflecting an unspecific increase of membranes due to lysosomal storage. According to these results no major biochemical differences were detectable between ISSD and nISSD. The nephrotic syndrome in nISSD could not be related to a general deficit in the sialylation of glycoproteins. Nevertheless, a cell membrane-specific alteration in sialoglycoproteins of glomerular cells might still be possible.

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Prenatal detection of Salla disease based upon increased free sialic acid in amniocytes

Renlund

Aula

Opitz³

et al. 1987

Am. J. Med. Genet.

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Salla disease is an autosomal recessive lysosomal storage disease relatively common in the Finnish population. The main manifestations of more than 70 patients detected to date are severe psychomotor retardation and ataxia of early onset. Intracellular free N-acetylneuraminic acid (sialic acid) is increased 10-20-fold and localized in the lysosomes. Four pregnancies at risk were monitored by quantitation of free and total sialic acid in amniocytes and supernatant amniotic fluid by high-performance liquid chromatography. In 3 children results were normal. Free sialic acid content of the amniocytes from one affected child was 2.6 nmol/mg protein, which was approximately 5 times higher than that of the 3 unaffected children (0.3 to 0.8) and 14 control samples (0.3 to 0.9). The ratio of free/total sialic acid of the amniocytes also clearly distinguished the affected pregnancy (13.8%) from the unaffected (2.3-4.8%) and control individuals (1.8-5.3%). This represents the first successful prenatal identification of a patient with Salla disease and indicates that both free sialic acid and free/total sialic acid ratio should be monitored in pregnancies at risk for the disease.

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

Cited by 10 publications

References 9 publications

The effect ofd‐(+)‐glucosamine on levels of freeN‐acetylneuraminic acid and UDP‐N‐acetylhexosamines in infantile sialic acid storage disease (ISSD) fibroblasts

The effect ofd‐(+)‐glucosamine on levels of freeN‐acetylneuraminic acid and UDP‐N‐acetylhexosamines in infantile sialic acid storage disease (ISSD) fibroblasts

Storage material from urine and tissues in the nephropathic phenotype of infantile sialic acid storage disease

Prenatal detection of Salla disease based upon increased free sialic acid in amniocytes

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