The challenge of CDG diagnosis

• Published in: Molecular genetics and metabolism 2019-01, Vol.126 (1), p.1-5
• Main Authors: Francisco, R., Marques-da-Silva, D., Brasil, S., Pascoal, C., dos Reis Ferreira, V., Morava, E., Jaeken, J.
• Format: Article
• Language: English
• Subjects: CDG; Diagnosis; Molecular testing; NGS; Whole Exome Sequencing
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2018.11.003

Congenital disorders of glycosylation (CDG) are a rapidly growing family of genetic diseases that currently includes some 130 different types. CDG diagnosis is a challenge, not only because of this large number but also because of the huge clinical heterogeneity even within a number of CDG. In addition, the classical screening test, serum transferrin isoelectrofocusing, is only positive in about 60% of CDG, and can even become negative in some CDG particularly in PMM2-CDG, the most frequent N-glycosylation defect. In order to facilitate CDG diagnosis, we hereby provide some practical tools: (1) a list of clinical features strongly suggestive of a distinctive CDG; (2) a table of clinical, biochemical and laboratory findings reported in CDG, arranged per organ/system; (3) an overview of the affected organs/systems in each CDG; and (4) a diagnostic decision tree in face of a patient with a suspicion of CDG. Most important is to keep in mind a CDG in any unexplained syndrome, in particular when there is neurological involvement. This mini-review enumerates clinical and biochemical hallmarks of these diseases and the biochemical and genetic testing available, and provides an updated list and information on identified CDG. The main aim is to act as a CDG diagnosis simplified guide for healthcare professionals and, additionally, as an awareness and lobbying tool to help in the effectiveness and promptness of CDG diagnosis.