Pediatric Liver Disease Patients and Secondary Glycosylation Abnormalities

Abstract

Background: Isoelectric focusing (IEF) of serum transferrin (Tf) is still the method of choice for diagnosis of congenital disorders of glycosylation (CDG). An abnormal glycosylation is also a known phenomenon in adult liver disease patients. The aim of this study was to characterize glycosylation disturbances in pediatric patients with primary liver disease. However, there are no reports of this phenomenon in children.Materials and Methods: Between 1995 and 2019, circa 2,000 serum Tf isoform analyses have been performed in children with primary liver diseases; some of them underwent subsequent analyses. We enrolled in this study 19 patients who developed an acute liver injury (ALI)/failure (ALF) or exhibited a chronic liver disease (CLD) and were evaluated and listed for liver transplantation (LTx) or had just undergone this procedure, and secondary abnormal serum Tf isoform profile.Results: Among 12 patients with ALI/ALF, 10 had an increased percentage of asialo-, monosialo-, and disialo-Tf isoforms. All patients with CLD had an increased percentage of asialo- and monosialo-Tf isoform. Two patients diagnosed with recurrent ALF had very specific serum Tf profile with a huge increase in the asialo- and monosialo-Tf isoform. On follow-up analyses (available in some patients), serum Tf IEF profile normalized in parallel to normalization of liver function tests, spontaneously or during treatment, including glucocorticosteroids in AIH, LTx in CLD.Conclusions: All pediatric patients with primary liver disease had increased asialo-Tf as well as monosialo-Tf isoforms. None of them had elevated percentage of trisialo-Tf isoform.

Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test

“…An abnormal TIEF test was identified in 26% of the patients, including increased a percentage of trisialotransferrin (70%), monosialotransferrin (17%), disialotransferrin (4%) and mixed transferrin isoforms (11%) [18]. None of the patients had a CDG diagnosis [18]. There is no information for neurological phenotypes of those patients and trisiaolotransferrin is not one of the typical CDG type I or II patterns.…”

“…In a recent study, glycosylation was studied in 981 patients with adult liver disease to investigate if there was any difference between primary and secondary glycosylation defects in liver disease. An abnormal TIEF test was identified in 26% of the patients, including increased a percentage of trisialotransferrin (70%), monosialotransferrin (17%), disialotransferrin (4%) and mixed transferrin isoforms (11%) [18]. None of the patients had a CDG diagnosis [18].…”

“…There is no information for neurological phenotypes of those patients and trisiaolotransferrin is not one of the typical CDG type I or II patterns. The study had no information regarding the underlying causes of liver disease [18]. In another study, 19 pediatric liver disease patients underwent a TIEF test [19]; 17 of them had elevated asialotransferrin and monosialotransferrin, and 13 of them had elevated disialotransferrin.…”

Congenital Disorders of Glycosylation: What Clinicians Need to Know?

“…It is also known that untreated patients with classic galactosemia (galactose-1-phosphate uridyltransferase deficiency) and fructosemia (fructose 1-phosphate aldolase deficiency) have secondarily an abnormal serum Tf isoform profile that could resemble CDG-I. For example, Bogdańska et al reported a study on 19 pediatric patients with primary liver disease and increased secondary asialo-Tf and monosialo-Tf isoforms; none of the patients had an elevated level of trisialo-Tf isoform (97). On the other hand, Jansen et al published a study about secondary glycosylation defects in 961 adult patients qualified for LTx or with chronic liver disease.…”

Transferrin isoform analysis from dried blood spots and serum samples by gel isoelectric focusing for screening congenital disorders of glycosylation

“…In some neonatal cases, it has been reported that the serum transferrin cathode fractions are slightly elevated, (mainly asialo-, monosialo-and sometimes also disialotransferrins), resembling a mild type II pattern (Peanne et al, 2018). Hypoglycosylation has been observed in patients with impaired liver function and infections with neuraminidase-producing microorganisms (Jaeken et al, 2017;Jansen et al, 2020, Bogdańska et al, 2021.…”