The screening by isoelectric focusing of transferrin for the diagnosis of congenital disorders of glycosylation

Background: Congenital Disorders of Glycosylation (CDG) are a group of inherited metabolic disorders caused by the defect in various steps in the biosynthesis of glycoproteins and other glycoconjugates. Material and methods: 40 patients under clinical suspicions for CDG at the Institute of Mother and Child were examined by isoelectric focusing of transferrin (IEFT) in collaboration with RadboudUMC, Netherlands and U.S.A. The spectrum of clinical presentations of these patients was multisystem damage, predominantly neurological manifestations. Results: Most of the patients (55%) had early neurological manifestations from the birth, such as hypotonia, psychomotor disability, cerebral MRI abnormalities, seizures (25%), cutis laxa (17.5%), total alopecia (2.5%), abnormal fat pads (2.5%), myopia (7.5%), nystagmus (5%), strabismus (2.5%), stroke-like episodes (2.5.%), ataxia (7.5%), abnormal coagulation (10%), hepatomegaly (35%) and liver cirrhosis (2.5%). Serum samples analyzed by IEFT showed the results: 37 normal, 2 questionable and 1 abnormal patterns. Two samples questionable belongs to the patients with Galactosemia and Fructosemia, which give the false-positive results. The last positive sample is performed additionally for glycomics profiling. In some cases, with IEFT negative profile was performed genetic test and were diagnosed other diseases, mimicking CDG, such as: NARP syndrome, late diagnosed PKU, GSD, Manosidoses, Prader-Willi Syndrome and chromosomal aberrations. Conclusions: The CDG is a rare metabolic disease with multisystem impairment and variety of symptoms which determine overlapping of phenotype with other genetic disorders. The process of diagnosis is very complex and can take several years