Abstract
Congenital disorders of glycosylation (CDGs) are a heterogeneous group of disorders with impaired glycosylation of proteins and lipids. These conditions have multisystemic clinical manifestations, resulting in gradually progressive complications including skeletal involvement and reduced bone mineral density. Contrary to PMM2-CDG, all remaining CDG, including ALG12-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, PGM3-CDG, CSGALNACT1-CDG, SLC35D1-CDG and TMEM-165, are characterized by well-defined skeletal dysplasia. In some of them, prenatal-onset severe skeletal dysplasia is observed associated with early death. Osteoporosis or osteopenia are frequently observed in all CDG types and are more pronounced in adults. Hormonal dysfunction, limited mobility and inadequate diet are common risk factors for reduced bone mineral density. Skeletal involvement in CDGs is underestimated and, thus, should always be carefully investigated and managed to prevent fractures and chronic pain. With the advent of new therapeutic developments for CDGs, the severity of skeletal complications may be reduced. This review focuses on possible mechanisms of skeletal manifestations, risk factors for osteoporosis, and bone markers in reported paediatric and adult CDG patients.
Highlights
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Congenital Disorders of Glycosylation (CDGs) are a clinically heterogenous group of over 150 diseases caused by defects in different steps of glycan metabolism pathways [1,2].These genetic disorders are characterized by an impaired synthesis and attachment of glycans to glycoproteins and glycolipids, and impaired synthesis of glycosylphosphatidylinositol (GPI) (Figure 1) [1]
This review describes skeletal manifestations and bone mineral density abnormalities in paediatric and adult Congenital disorders of glycosylation (CDGs) patients with the aim to discuss the heterogeneity of clinical manifestations and correlate the genetic data with observed skeletal phenotype to evaluate the potential mechanism of mutational effect on the phenotype
Anterior spine x-ray a 25-year-old female patient affected with PMM2-CDG; bone mineral density is below expected for her age (T score −2.6, z-score −2.6); (b) lateral view; (c) radiological features of her mineral density is below expected for her age (T score −2.6, z-score −2.6); (b) lateral view; (c) radiological features of lumbar spine: there is a double mild curve scoliosis and no rotational deformity
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Congenital Disorders of Glycosylation (CDGs) are a clinically heterogenous group of over 150 diseases caused by defects in different steps of glycan metabolism pathways [1,2] These genetic disorders are characterized by an impaired synthesis and attachment of glycans to glycoproteins and glycolipids, and impaired synthesis of glycosylphosphatidylinositol (GPI) (Figure 1) [1]. As. Glycosylation a variety of posttranslational biological processes including a result, CDG patients with very diverse clinical phenotypes, with multi-system main components of thepresent hormone cascades regulating growth and metabolism [5,6]. As a involvement [4,5,6,7] These include cognitive impairment, neurological (epilepsy, hypotonia, result, CDG patients present with very diverse clinical phenotypes, with multi-system inataxia and polyneuropathy), ophthalmological, skeletal, cardiac, hepatic, haematological volvement [4,5,6,7]. This review describes skeletal manifestations and bone mineral density abnormalities in paediatric and adult CDG patients with the aim to discuss the heterogeneity of clinical manifestations and correlate the genetic data (causative genes) with observed skeletal phenotype to evaluate the potential mechanism of mutational effect on the phenotype
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