The congenital disorders of glycosylation: A multifaceted group of syndromes

Abstract

Summary:The congenital disorders of glycosylation (CDG) are a rapidly expanding group of metabolic syndromes with a wide symptomatology and severity. They all stem from deficient N-glycosylation of proteins. To date the group contains 18 different subtypes: 12 of Type I (disrupted synthesis of the lipid-linked oligosaccharide precursor) and 6 of Type II (malfunctioning trimming/processing of the protein-bound oligosaccharide). Main features of CDG involve psychomotor retardation; ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features, including inverted nipples and subcutaneous fat pads; and strabismus. No treatment currently is available for the vast majority of these syndromes (CDG-Ib and CDG-IIc are exceptions), even though attempts to synthesize drugs for the most common subtype, CDG-Ia, have been made. In this review we will discuss the individual syndromes, with focus on their neuronal involvement, available and possible treatments, and future directions.

Congenital disorder of glycosylation type Ia: a non-progressive encephalopathy associated with multisystemic involvement

“…The patient did not have hypotonia or short stature, two of the most frequent findings in CDG-Ia 8,19 . In addition, she did not have abnormal subcutaneous fat deposition, with "fat pad" on the buttocks, which suggests the diagnosis 7 .…”

Understanding Human Glycosylation Disorders: Biochemistry Leads the Charge

“…Previously, the genes responsible for most glycosylation disorders were identified by biochemical analysis of fibroblasts and serum glycans (8,25). Now, genetic mapping techniques have largely replaced this approach (1,7,8).…”

Insights into complexity of congenital disorders of glycosylation

“…In addition, several CDGs of so far unknown etiology (CDG-x) have been recognized. CDG symptoms highly vary, but some are common for several CDG types, such as psychomotor retardation, failure to thrive, coagulopathies, dysmorphic features, seizures and stroke-like episodes (9,10). Clinical manifestation of CDGs ranges from very mild to extremely severe (literately, all organs can be affected).…”