Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic disorders caused by a defect in the process of protein glycosylation. In this work, we present a comprehensive glycoprofile analysis of a male patient with a novel missense variant in the SLC35A2 gene, coding a galactose transporter that translocates UDP-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi apparatus. Isoelectric focusing of serum transferrin, which resulted in a CDG type II pattern, was followed by structural analysis of transferrin and serum N-glycans, as well as the analysis of apolipoprotein CIII O-glycans by mass spectrometry. An abnormal serum N-glycoprofile with significantly increased levels of agalactosylated (Hex3HexNAc4-5 and Hex3HexNAc5Fuc1) and monogalactosylated (Hex4HexNAc4 ± NeuAc1) N-glycans was observed. Additionally, whole exome sequencing and Sanger sequencing revealed de novo hemizygous c.461T > C (p.Leu154Pro) mutation in the SLC35A2 gene. Based on the combination of biochemical, analytical, and genomic approaches, the set of distinctive N-glycan biomarkers was characterized. Potentially, the set of identified aberrant N-glycans can be specific for other variants causing SLC35A2-CDG and can distinguish this disorder from the other CDGs or other defects in the galactose metabolism.

Ornithine transcarbamylase (OTC) deficiency is the most common inherited metabolic disorder in urea cycles with an incidence of 1:14,000 live births. Pregnancy, childbirth and the postpartum period are considered challenging for women with this hereditary metabolic disorder, with a risk of hyperammonemia, especially in the first week after delivery. In our article, we discuss severe hepatic failure, a pregnancy complication in an OTC deficient patient that has not previously been published. Firstly, our aim is to highlight the need for a strict adherence to the recommendation of the gradual increase of protein intake during pregnancy and the importance of multidisciplinary monitoring of pregnant patients with OTC deficiency. Secondly, we refer to critical postpartum hyperammonemia in patients with this hereditary metabolic disorder.

Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive defect of L-isoleucine catabolism caused by pathogenic variants in the ACADSB gene. While early reports described neurological symptoms, expanded newborn screening cohorts have revealed predominantly asymptomatic individuals, raising questions regarding the clinical significance and optimal management. We performed an evaluation of three probands with a biochemical profile consistent with SBCADD identified in a Central European country. Acylcarnitines were measured by liquid chromatography with tandem mass spectrometry, urinary organic acids by gas chromatography with mass spectrometry, and ACADSB was sequenced. Clinical data were collected from regional paediatric follow-up. Three individuals with a biochemical profile consistent with SBCADD were identified in Slovakia. Two were detected through newborn screening, whereas one was diagnosed at 5 years of age. All three showed elevated C5-acylcarnitine; the C5/C8 ratio was increased in two patients, while in the third it remained within the reference range despite persistently elevated C5. Urinary 2-methylbutyrylglycine and 2-ethyl-3-hydroxypropionate were elevated in all cases and showed intra-individual variability; in one sample, 2-methylbutyrylglycine remained increased while 2-ethyl-3-hydroxypropionate had normalised. Two patients carried pathogenic ACADSB variants (one homozygous splice-site variant c.303 + 1G > A, one compound heterozygous for p.Thr148Ile and p.Glu387Lys), whereas genetic testing was not performed in the third case. Over the available follow-up period, no episodes of metabolic decompensation were observed; two patients remained clinically well, and one patient had autism spectrum disorder. Free carnitine concentrations were within the reference range in all probands. Our findings support SBCADD as a primarily biochemical phenotype with a largely benign course, while illustrating variability of urinary biomarkers and C5/C8 ratios. Accurate differentiation from isovaleric acidemia and careful integration of biochemical, genetic and clinical data remain essential.