RFT1 is an enzyme involved in glycosylation pathway. Its defect causes one of the CDG syndromes. So far there were described six patients all up to the age of six. We present clinical, biochemical and molecular findings of two siblings with RFT1-CDG. First is 18 years old boy with severe mental retardation, profound bilateral hearing loss, epilepsy, obesity, craniofacial dysmorphy, hypothyreosis and mild coagulopathy. His sister is 16 and shows similar symptoms; just the hearing problems are milder. Both patients showed abnormal a type 1 transferrin isofocusing pattern. LLO analysis showed accumulation of DolPP-GlcNAc2Man5 at the cytosolic side of the ER membrane. Molecular analysis revealed two novel heterozygous missense mutations (c.1222A>G/c.1325 G>A) in the 12th exon of RFT1 gene. Our patients show milder phenotype and longer survival compare to the previously published patients. Several glycoproteins are essential in the normal production and regulation of thyroid hormones, including TSH, TBG, thyreoglobuline and the thyroid receptor. We prospectively examined glycosylation, the endocrine and clinical aspects of thyroid function, energy expenditure, and evaluated growth and development in 32 patients with congenital disorders of glycosylation. Thyroid function was abnormal in 19 patients with consistently elevated TSH in ten children, mostly in PMM2-CDG. In four patients, TSH elevations resolved without intervention. Enzymatic desialylation of TBG and TSH had no effect on the laboratory results in these patients and controls. Low free thyroxine was noted in three patients, corresponding to decreased energy expenditure and weight-increase. Low TBG was noted in half of the patients. Thyroid function tests in CDG patients are often abnormal. Most patients appeared to be clinically euthyroid even in the presence of abnormal TBG and TSH values. Still, in certain cases of significantly elevated TSH or low FT4, manifesting in clinical hypothyreoidism, thyroxine supplementation was necessary. TBG deficiency did not appear to have any clinical consequences. Hypoglycosylation of thyroid-proteins may affect laboratory values but may not always be of clinical importance for patients. Measuring energy expenditure in patients helps to decide on the appropriate therapeutic approach. Isoelectric focusing of transferrin and apolipoprotein CIII are used to diagnose N-linked and / or core-1-and 2 O-linked glycosylation defects. Plasma 2D-PAGE studies revealed altered charge and mass forms of C1inhibitor in CDG I and II patients. C1-Inhibitor is a protease inhibitor that plays a crucial role in various physiological pathways. It is heavily glycosylated: 49% of its molecular weight (MW) is composed of six Nand seven core-1 O-glycans. Investigations of C1-inhibitor as a potential marker for both N-& O-linked glycosylation defects was performed on patients with CDG type I and II, including congenital muscular dystrophies, by Western blotting. CDG I cases revealed reduced intensity of the native 100 kDa MW band and a lower MW band. In the CDG II group, samples from patients with FKRP and POMGnT1 mutations showed a normal profile (as expected as these are defects in Omannosylation). However, reduced MW bands were observed in the plasma from a patient with a LARGE mutation (which have defects in both O-mannose and O-GalNAc glycosylation) and also from a muscular dystrophy patient of undefined genetic cause. This demonstrates C1inhibitor could be a combined potential marker for various N-and Oglycosylation disorders. SLC35A1-CDG has been described in a single patient with spontaneous massive bleedings in the posterior chamber of the right eye, cutaneous and pulmonary hemorrhages, thrombocytopenia, neutropenia and recurrent infections. This new type of congenital disorder of glycosylation affects the transport of CMP-sialic acid into the Golgi apparatus. Due to the lethal outcome in the initial patient the genetic background could not be fully confirmed. We evaluated a patient of consanguineous origin, presenting with multiple dysmorphic features, psychomotor retardation, thrombocytopenia, persistent proteinuria and aortic insufficiency. Isoelectric focusing of transferrin showed a type II pattern, while the apolipoprotein C-III isofocusing pattern was normal. Mass spectrometry of serum N-glycans demonstrated severely abnormal sialylation. Mutation analysis in SLC35A1 confirmed a homozygous missense mutation. Functional analysis of the mutations in a CMP-sialic acid transporter assay in yeast showed a 50% reduction in transport activity. Expression studies showed significant gene expression in the central nervous system, and the kidneys, comparable with mental retardation and chronic proteinuria in our patient. We report on the second SLC35A1-CDG, and first adult, patient, presenting with intellectual disability, thrombocytopenia, renal and cardiac involvement due to a CMP-sialic acid transporter defect. The bleeding disorder remained asymptomatic until adulthood.