Secondary alteration of the transferrin isoelectric focusing pattern in a case of bacterial meningitis

Abstract

Congenital disorders of glycosylation (CDG) are a group of inherited defects in the synthesis and processing of the linked glycans of glycoproteins and other glycoconjugates. The phenotypic spectrum presents wide variability, and clinical diagnosis is not reliable in most cases. Isoelectric focusing (IEF) of serum transferrin is widely used as a tool to detect CDG. We describe a paediatric patient presenting an altered serum transferrin pattern due to a secondary disorder of glycosylation caused by pneumococcal meningitis (Streptococcus pneumoniae, serotype 19A). During admission, brain CT scan and MRI showed acute ischaemic lesions in brain frontotemporal parenchyma, and enlarged subarachnoidal spaces in the frontal area resembling a chronic injury. This led us to screen for inborn errors of metabolism potentially associated with these findings (homocystinuria, glutaric aciduria, CDG syndromes). Biochemical studies for the screening of these inborn errors of metabolism were normal except for sialotransferrin isoelectric focusing, which showed a type 2 pattern. However, 16 days later, together with the remission of the meningitis process, the sialotransferrin pattern had normalized. The apolipoprotein C-III (an O-glycoprotein) profile was normal in all samples analysed. In conclusion, infectious events should be ruled out in the differential diagnosis of CDG syndromes. Furthermore, our findings highlight the possibility that the type 2 IEF pattern of serum sialotransferrin detected in some patients with neonatal death due to organ failure and septic events might be secondary to the infectious process.

Global serum glycoform profiling for the investigation of dystroglycanopathies & Congenital Disorders of Glycosylation

“…While serum transferrin IEF has proven to be a useful test for defective N -glycosylation [5] , it only identifies differences in charge and lacks information on changes in molecular weight (MW). In addition, secondary glycosylation disorders including galactosaemia, hereditary fructose intolerance, bacterial infections [16] and transferrin polymorphisms must be excluded before considering a diagnosis of CDG. Other methods of CDG investigation include isoelectric focusing of other glycoproteins or investigation of the total glycan profile from glycans removed from the glycoproteins using PNGase F digestion and MALDI analysis [17] .…”

The effect of malnutrition on protein glycosylation in childhood

“…Protein glycosylation, a result of many complex reactions in Golgi and endoplasmic reticulum [ 1 ] , is closely related to physiological processes such as cell adhesion, migration, cell growth and cell differentiation [ 2 ] . Therefore, defects in glycosylation are associated with several pathological conditions including inflammation, rheumatoid arthritis, cancer, liver diseases [ 3 ] , galactosemia and fructosemia [ 4 ] , sepsis [ 5 ] , bacterial meningitis [ 6 ] , drugs [ 7 ] and chronic alcohol abuse [ 8 , 9 ] in addition to congenital disorders of glycosylation [ 10 - 12 ] .…”