Inhibitory effect of free sialic acid on complement activation and its significance in hypocomplementemic glomerulonephritis

Abstract Background Infantile free sialic acid storage disease (ISSD) is a severe multisystemic disorder characterized by the accumulation of free sialic acid in lysosomes. Case presentation The patient presented prenatally with fetal ascites and large scrotal hernias, without pleural or pericardial effusion. During the infantile period, he was diagnosed with permanent isolated immunoglobulin G (IgG) hypogammaglobulinemia, which thus far has rarely been associated with ISSD. The analysis of the SLC17A5 gene revealed a novel homozygous 94 bp gene deletion. We further provide a detailed description of pre- and postnatal clinical and radiographic findings. Conclusions Fetal ascites could be the first sign of several lysosomal storage diseases (LSDs), including ISSD. The analysis of LSD gene panels is an effective approach to diagnosis in the case of non-specific symptoms and when specific biochemical tests are not easily available.

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Correction of the Delayed Fibrin Aggregation of Fetal Fibrinogen by Partial Removal of Sialic Acid

10.1055/s-0039-1684458 ◽

1979 ◽

Author(s):

D.K. Galanakis ◽

M.W. Mosesson

Keyword(s):

Sialic Acid ◽

Acid Content ◽

Acid Value ◽

Full Term ◽

Thrombin Time ◽

Sialic Acid Content ◽

Vibrio Cholera ◽

The Mean ◽

Fraction I ◽

Free Sialic Acid

Human umbilical oord fibrinogen characteristically displays delayed fibrin aggregation under conditions of relatively high ionic strength. This delay is greater in fibrinogen obtained from premature (p) (24–35 weeks gestation) infants, as compared with that from full term (FT) infants. We compared the sialic acid content of (fraction I-2) fetal (P and FT) with adult (A) fibrinogen, obtained from pooled plasma. The mean sialic acid μg/100mg protein) values were: P, 818 (±135 SD, range 621–1030); FT, 720 (±212, range 505–1280); A, 626 (±110, range 487-806). One P fibrinogen preparation (thrombin time 22.6 seconds) was partially desialated (resulting sialic acid value 490) by incubation with Vibrio cholera neuraminidase, dialyzed , and precipitated with ethanol to remove free sialic acid. The thrombin time of the resulting preparation was 15.4 (range 15.2–15.8), compared to 16.1 (range 15.5–16.4) for untreated A fibrinogen. The results suggest that the delayed fibrin aggregation of fetal fibrinogen is attributable to its relatively high sialic acid content. Moreover, the intermediate sialic acid (and thrombin time) values of FT (as compared to those of p) fibrinogen intimate the presence of a mixture of adult and fetal fibrinogen in full term cord blood.

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Phenotypic Variation and Magnetic Resonance Imaging (MRI) in Salla Disease, a Free Sialic Acid Storage Disorder

Neuropediatrics ◽

10.1055/s-2008-1073028 ◽

1994 ◽

Vol 25 (05) ◽

pp. 238-244 ◽

Cited By ~ 35

Author(s):

Leena Haataja ◽

R. Parkkola ◽

P. Sonninen ◽

S. Vanhanen ◽

J. Schleutker ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Sialic Acid ◽

Magnetic Resonance ◽

Phenotypic Variation ◽

Resonance Imaging ◽

Salla Disease ◽

Storage Disorder ◽

Magnetic Resonance Imaging Mri ◽

Free Sialic Acid

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

American Journal of Medical Genetics ◽

10.1002/ajmg.1320280216 ◽

1987 ◽

Vol 28 (2) ◽

pp. 377-384 ◽

Cited By ~ 13

Author(s):

Martin Renlund ◽

Pertti Aula ◽

John M. Opitz ◽

James F. Reynolds

Keyword(s):

Sialic Acid ◽

Prenatal Detection ◽

Salla Disease ◽

Free Sialic Acid

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Compstatin Inhibits Complement and Cellular Activation in Whole Blood in Two Models of Extracorporeal Circulation

Blood ◽

10.1182/blood.v92.5.1661 ◽

1998 ◽

Vol 92 (5) ◽

pp. 1661-1667 ◽

Cited By ~ 101

Author(s):

Bo Nilsson ◽

Rolf Larsson ◽

Jaan Hong ◽

Graciela Elgue ◽

Kristina Nilsson Ekdahl ◽

...

Keyword(s):

Extracorporeal Circulation ◽

Complement Activation ◽

Whole Blood ◽

Polymer Surface ◽

Inhibitory Effect ◽

Cell Counts ◽

Complement Component C3 ◽

Precursor Peptide ◽

Extracorporeal Circuits ◽

American Society

Abstract Recently, a C3-binding cyclic synthetic peptide (Compstatin) has been identified that binds to complement component C3 and inhibits complement activation. Here we have examined the influence of Compstatin on complement activation and its indirect effects on cellular responses in whole blood in two models for extracorporeal circulation. Compstatin effectively inhibited the generation of C3a and sC5b-9 and the binding of C3/ C3 fragments to the polymer surface. As a result of the inhibition of complement activation, the activation of polymorphonuclear leukocytes (PMNs; as assessed by the expression of CD11b) and the binding of these cells (CD16+) to the polymer surface were almost completely lost. In contrast, blood cell counts were not affected. Using surface plasmon resonance technology, we have confirmed that Compstatin exerts its inhibitory effect on complement activation by binding to native C3. These data show that complement activation, leading to activation and binding of PMNs to the biomaterial surface, can be abolished by the addition of Compstatin. The properties of Compstatin make Compstatin a promising drug for use in extracorporeal circuits to avoid bioincompatibility reactions, eg, during cardiopulmonary bypass, but also a favorable precursor peptide for the development of an anticomplement drug for oral use. © 1998 by The American Society of Hematology.

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