Fiumara, Agata

AbstractCongenital disorders of glycosylation are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid glycan biosynthesis. These disorders mostly manifest with multisystem involvement. Individuals with ALG8‐CDG commonly present with hypotonia, protein‐losing enteropathy, and hepatic involvement. Here, we describe seven unreported individuals diagnosed with ALG8‐CDG based on biochemical and molecular testing and we identify nine novel variants in ALG8, bringing the total to 26 individuals with ALG8‐CDG in the medical literature. In addition to the typical multisystem involvement documented in ALG8‐CDG, our cohort includes the two oldest patients reported and further expands the phenotype of ALG8‐CDG to include stable intellectual disability, autism spectrum disorder and other neuropsychiatric symptoms. We further expand the clinical features in a variety of organ systems including ocular, musculoskeletal, dermatologic, endocrine, and cardiac abnormalities and suggest a comprehensive evaluation and monitoring strategy to improve clinical management.

Abstract Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1‐CDG. PGM1‐CDG usually manifests as a multisystem disease. Most patients present as infants with cleft palate, liver function abnormalities and hypoglycemia, but some patients present in adulthood with isolated muscle involvement. Some patients develop life‐threatening cardiomyopathy. Unlike most other CDG, PGM1‐CDG has an effective treatment option, d ‐galactose, which has been shown to improve many of the patients' symptoms. Therefore, early diagnosis and initiation of treatment for PGM1‐CDG patients are crucial decisions. In this article, our group of international experts suggests diagnostic, follow‐up, and management guidelines for PGM1‐CDG. These guidelines are based on the best available evidence‐based data and experts' opinions aiming to provide a practical resource for health care providers to facilitate successful diagnosis and optimal management of PGM1‐CDG patients.

Abstract Phosphomannomutase 2 (PMM2‐CDG) is the most common congenital disorder of N‐glycosylation and is caused by a deficient PMM2 activity. The clinical presentation and the onset of PMM2‐CDG vary among affected individuals ranging from a severe antenatal presentation with multisystem involvement to mild adulthood presentation limited to minor neurological involvement. Management of affected patients requires a multidisciplinary approach. In this article, a systematic review of the literature on PMM2‐CDG was conducted by a group of international experts in different aspects of CDG. Our managment guidelines were initiated based on the available evidence‐based data and experts' opinions. This guideline mainly addresses the clinical evaluation of each system/organ involved in PMM2‐CDG, and the recommended management approach. It is the first systematic review of current practices in PMM2‐CDG and the first guidelines aiming at establishing a practical approach to the recognition, diagnosis and management of PMM2‐CDG patients.