Endocrine Implications of Congenital Disorders of Glycosylation

Abstract

Glycosylation, attachment of monosaccharides or glycans to specific residues of proteins and lipids, is the most common post-translational modification. Defects among glycoprotein synthesis or modification pathways result in a genetically and clinically heterogenous group of metabolic disorders, congenital disorders of glycosylation (CDGs) with an estimated prevalence of 1/10,000. CDGs have multisystem involvement in which significant neurological dysfunction is frequent, with variable impairment of other organ functions. Most of the proteins responsible for endocrine homeostasis are essentially glycoproteins so disorders of glycosylation have an impact on hormone secretory pathways, changing hormone and carrier protein stability, circulatory half-live and abundance, alternating receptor configuration, activation, hormone-substrate affinity, and resetting endocrine control and feedback loops. Endocrine implications of CDGs are extensive and are described in up to 55% of all patients with CDGs during the natural course of the disease. This frequency is increased up to 85% in some CDG subgroups. Impacts on growth and growth factors, thyroid hormones, hypothalamo-pituitary-adrenal axis, hypothalamo-pituitary-gonadal axis, glucose metabolism, bone health and prolactin have been reported, yet clinical studies are scarce, with data mostly derived from case series. The aim of this review is to describe the current understanding of the endocrine implications of CDGs, focusing on both preclinical and clinical studies, highlighting the broad spectrum of findings. Clinical and laboratory findings of CDGs and the effect of current treatment strategies on endocrine function will be briefly discussed.