As the name suggests, Congenital Disorders of Glycosylation (CDGs) are in-born errors of metabolism caused by enzymatic defects in the highly conserved biochemical process of N-linked glycosylation. This process involves the synthesis and processing of (N)-linked glycans or oligosaccharides on glycoproteins. CDGs are classified into two types: type I CDGs are concerned with defects in the synthesis of the lipid-linked oligosaccharide (LLO) chain or its transfer to the protein, while type II CDGs involve disruptions in the terminal portion of the glycosylation pathway, namely the processing of the LLO chain bound to the protein.
CDG1N is a type I disorder with an infantile-onset. Affected patients suffer from severe developmental delay, hypotonia, myoclonic jerks, seizures, ataxia, spasticity and hyperreflexia. Infants exhibit feeding difficulties and may fail to thrive. Other symptoms include respiratory insufficiency, short stature, microcephaly, micrognathia, sensorineural deafness, loss of visual acuity, adducted thumbs and valgus foot deformity. Some patients have been reported to suffer from coagulopathy and hepatomegaly.
The disorder is diagnosed based on isoelectric focusing studies or capillary electrophoresis to detect a type I pattern of transferrin isoforms. It is further confirmed by genetic analysis of the RFT1 gene. There is currently no cure for the condition and treatment is focused on symptomatic care and the prevention of secondary complications.
Monies et al. (2017) studied the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 3-year-old male from a consanguineous family, presented with congenital microcephaly, global developmental delay, epilepsy and hematemesis. Using whole exome sequencing, a homozygous mutation (c.775+1G>C) was identified in exon 7 of the patient’s RFT1 gene, associated with CDG1N. Given the atypical presentation of the patient, this case helped in the phenotypic expansion of the disorder.