ABSTRACT
Congenital disorders of glycosylation (CDG) are due to defective glycosylation of glycoconjugates. Conserved oligomeric Golgi (COG)-CDG are genetic diseases due to defects of the COG complex subunits 1-8 causing N-glycan and O-glycan processing abnormalities. In COG-CDG, isoelectric focusing separation of undersialylated glycoforms of serum transferrin and apolipoprotein C-III (apoC-III) allows to detect N-glycosylation and O-glycosylation defects, respectively. COG5-CDG (COG5 subunit deficiency) is a multisystem disease with dysmorphic features, intellectual disability of variable degree, seizures, acquired microcephaly, sensory defects and autistic behavior. We applied matrix-assisted laser desorption/ionization-MS for a high-throughput screening of differential serum O-glycoform and N-glycoform in five patients with COG5-CDG. When compared with age-matched controls, COG5-CDG showed a significant increase of apoC-III0a (aglycosylated glycoform), whereas apoC-III1 (mono-sialylated glycoform) decreased significantly. Serum N-glycome of COG5-CDG patients was characterized by the relative abundance of undersialylated and undergalactosylated biantennary and triantennary glycans as well as slight increase of high-mannose structures and hybrid glycans. Using advanced and well-established MS-based approaches, the present findings reveal novel aspects on O-glycan and N-glycan profiling in COG5-CDG patients, thus providing an increase of current knowledge on glycosylation defects caused by impairment of COG subunits, in support of clinical diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.
Subject(s)
Adaptor Proteins, Vesicular Transport/blood , Congenital Disorders of Glycosylation/blood , Biomarkers/blood , Case-Control Studies , Child , Congenital Disorders of Glycosylation/diagnosis , Glycosylation , High-Throughput Screening Assays/methods , Humans , Polysaccharides/blood , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
The group of congenital disorders of glycosylation (CDG) has expanded tremendously since its first description in 1980, with around 70 distinct disorders described to date. A great phenotypic variability exists, ranging from multisystem disease to single organ involvement. Skin manifestations, although inconsistently present, are part of this broad clinical spectrum. Indeed, the presence of inverted nipples, fat pads and orange peel skin in a patient with developmental delay are considered as a hallmark of CDG, particularly seen in PMM2 deficiency. However, over the years many more dermatological findings have been observed (e.g., ichthyosis, cutis laxa, tumoral calcinosis ). In this review we will discuss the variety of skin manifestations reported in CDG. Moreover, we will explore the possible mechanisms that link a certain glycosylation deficiency to its skin phenotype.
