Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

Abstract

An ever-increasing number of disturbances in glycosylation have been described to underlie certain unexplained liver diseases presenting either almost isolated or in a multi-organ context. We aimed to update previous literature screenings which had identified up to 23 forms of congenital disorders of glycosylation (CDG) with associated liver disease. We conducted a comprehensive literature search of three scientific electronic databases looking at articles published during the last 20 years (January 2000-October 2020). Eligible studies were case reports/series reporting liver involvement in CDG patients. Our systematic review led us to point out 41 forms of CDG where the liver is primarily affected (n ¼ 7) or variably involved in a multisystem disease with mandatory neurological abnormalities (n ¼ 34). Herein we summarize individual clinical and laboratory presentation characteristics of these 41 CDG and outline their main presentation and diagnostic cornerstones with the aid of two synoptic tables. Dietary supplementation strategies have hitherto been investigated only in seven of these CDG types with liver disease, with a wide range of results. In conclusion, the systematic review recognized a liver involvement in a somewhat larger number of CDG variants corresponding to about 30% of the total of CDG so far reported, and it is likely that the number may increase further. This information could assist in an earlier correct diagnosis and a possibly proper management of these disorders.

A novel variant in ALG1 gene associated with congenital disorder of glycosylation: A case report and short literature review

“…Liver is a major site of glycosylation in the body to produce most of the glycosylated serum proteins, and therefore its disease may also affect the glycosylation process. However, alteration of glycosylation patterns can themselves primarily affect liver function, therefore, the screening for CDG should always be considered in patients with unexplained liver disease (Colantuono et al, 2021 ; Marques‐da‐Silva et al, 2017 ). A total of 10.71% of patients had renal involvement, manifested as congenital nephrotic syndrome.…”

Genetic aetiologies of acute liver failure

“…159 The spectrum can range from trivial elevation in transaminases, steatosis and hepatomegaly to chronic, liver disease and cirrhosis. 160,161 However, cases presenting with true ALF are limited to a small number of isolated reports of mannose phosphate isomerase (MPI)-CDG (type 1b) or suspected CDG based on transferrin isoelectric focusing but without genetic confirmation. 33,162 Even among the MPI-CDG characterised by a triad of digestive, hepatic and endocrine symptoms, liver disease is most frequently in the form of fibrosis and portal hypertension.…”

“…Liver involvement within CDGs is common and seen in about 22–30% of cases although the nature and extent of disease is highly variable 159 . The spectrum can range from trivial elevation in transaminases, steatosis and hepatomegaly to chronic, liver disease and cirrhosis 160,161 . However, cases presenting with true ALF are limited to a small number of isolated reports of mannose phosphate isomerase (MPI)‐CDG (type 1b) or suspected CDG based on transferrin isoelectric focusing but without genetic confirmation 33,162 .…”

Fatty liver disease in children (MAFLD/PeFLD Type 2): unique classification considerations and challenges

“…With increasing prevalence of fatty liver in children, there is a risk that children are falsely labelled as MAFLD when, in fact, the underlying reason for the fatty liver is an IMD. Furthermore, the list of such IMDs are increasing, including congenital disorders of glycosylation 6 and aminoacyl transfer RNA synthetase deficiencies 7 ( Figure 1 ). Clues that may point towards an underlying IMD include younger age (<5 years) and lean body habitus 4 ( Figure 2 ).…”