heparitin-sulfate and Seizures

Heparan sulfate proteoglycans are vital components of the extracellular matrix and are essential for cellular homeostasis. Many genes are involved in modulating heparan sulfate synthesis, and when these genes are mutated, they can give rise to early-onset developmental disorders affecting multiple body systems. Herein, we describe a consanguineous family of four sibs with a novel disorder, which we designate as seizures-scoliosis-macrocephaly syndrome, characterised by seizures, intellectual disability, hypotonia, scoliosis, macrocephaly, hypertelorism and renal dysfunction.. Our application of autozygosity mapping and whole-exome sequencing allowed us to identify mutations in the patients. To confirm the autosomal-recessive mode of inheritance, all available family members were genotyped. We also studied the effect of these mutations on protein expression and function in patient cells and using an in vitro system.. We identified two homozygous mutations p.Met87Arg and p.Arg95 Cys in exostosin 2, EXT2, a ubiquitously expressed gene that encodes a glycosyltransferase required for heparan sulfate synthesis. In patient cells, we observed diminished EXT2 expression and function. We also performed an in vitro assay to determine which mutation has a larger effect on protein expression and observed reduced EXT2 expression in constructs expressing either one of the mutations but a greater reduction when both residues were mutated.. In short, we have unravelled the genetic basis of a new recessive disorder, seizures-scoliosis-macrocephaly syndrome. Our results have implicated a well-characterised gene in a new developmental disorder and have further illustrated the spectrum of phenotypes that can arise due to errors in glycosylation.

Topics: Adult; Child, Preschool; Developmental Disabilities; Exostoses; Female; Heparitin Sulfate; Humans; Male; Mutation; N-Acetylglucosaminyltransferases; Pedigree; Seizures; Sequence Analysis, DNA

In the past 10 years numerous reports of cases referring to complications and their outcome with heparin-induced thrombocytopenia type II (HIT II) have been published. Clinically these symptoms are manifested as a combination of arterial and venous thromboembolisms. Mostly affected are the vessels of the limbs, the abdomen, kidneys and coronary arteries. We present the most rare initial manifestations of cerebral symptoms with headache, nausea, change of character and generalised convulsion, which have found their origin in sinus vein thrombosis and the treatment with the heparinoid danaparoid.

Topics: Aged; Anticoagulants; Anticonvulsants; Blood Cell Count; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Male; Mental Disorders; Postoperative Complications; Seizures; Sinus Thrombosis, Intracranial; Thrombocytopenia; Tomography, X-Ray Computed