No abstract

Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.

In addition to the main catabolic routes of tryptophan (Trp), there exist minor and less thoroughly investigated pathways; one of these leads to indolylacrylic acid (IAcrA). IAcrA is a plant growth hormone, whereas its biological role in animals is still obscure, as is the way and site where it is formed in the organism. A two-stage production is likely: Intestinal microorganisms catabolize Trp to indole derivatives which are then absorbed and converted to IAcrA and its glycine conjugate, indolylacryloylglycine (IAcrGly). Our finding of IAcrGly in the urine of proven germ-free piglets points to the possibility that Trp can be converted to IAcrA without the intervention of intestinal microorganisms. Seasonal and age variations, influence of light and connection with photodermatoses have been reported. Besides other pathological conditions the differences in IAcrGly excretion relative to normal controls were especially pronounced in some myopathies, namely in boys with Duchenne muscular dystrophy.

No abstract

The aim of this study is to report our 3years experience with the screening of congenital disorders of glycosylation. A common isoelectric focusing method with immunofixation was used for analysis of serum transferrin and α1-antitrypsin, apart from several other procedures. A group of about 1000 individuals, both healthy controls and patients, mostly with signs of a metabolic disease were examined. Here we present an overview of 1) hypoglycosylation findings, 2) distribution of protein variants, 3) misguiding rare Tf variants found in our set, and 4) association of some phenotypes with various diseases.