Biochemical testing for congenital disorders of glycosylation: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Abstract

Congenital disorders of glycosylation (CDG) are a large and continually expanding group of disorders that present with a variety of clinical findings and have been linked to over 170 genes. Individually, CDGs are rare; however, the true incidence may be underestimated because of the variability of the clinical findings, and the multiple testing strategies needed to diagnosis them across multiple pathways. Testing for CDGs has evolved over recent years with the availability of high-throughput molecular testing and improved gene discovery techniques. Biochemical testing to detect defects in glycosylated proteins or enzymatic deficiency still plays a critical role in the diagnosis of affected individuals, and both testing modalities are often required to finalize a diagnosis. Emerging therapeutic approaches targeting improvements in glycosylation require reliable and reproducible biochemical testing for therapeutic monitoring, dose adjustment, and avoidance of dose-related side effects. To maintain clinical sensitivity and specificity and to ensure reproducibility across laboratories performing complex biochemical testing, the American College of Medical Genetics and Genomics has developed the following technical standard.