Background The congenital disorders of glycosylation (CDG) are a heterogeneous group of rare metabolic diseases with multi-system involvement. The liver phenotype of CDG varies not only according to the specific disorder, but also from patient to patient. In this study, we sought to identify common patterns of liver injury among patients with a broad spectrum of CDG, and to provide recommendations for follow-up in clinical practice. Methods Patients were enrolled in the Frontiers in Congenital Disorders of Glycosylation natural history study. We analyzed clinical history, molecular genetics, serum markers of liver injury, liver ultrasonography and transient elastography, liver histopathology (when available), and clinical scores of 39 patients with 16 different CDG types (PMM2-CDG, n = 19), with a median age of 7 years (range: 10 months to 65 years). For patients with disorders which are treatable by specific interventions, we have added a description of liver parameters on treatment. Results Our principal findings are (1) there is a clear pattern in the evolution of the hepatocellular injury markers alanine aminotransferase and aspartate aminotransferase according to age, especially in PMM2-CDG patients but also in other CDG-I, and that the cholangiocellular injury marker gamma-glutamyltransferase is not elevated in most patients, pointing to an exclusive hepatocellular origin of injury; (2) there is a dissociation between liver ultrasound and transient elastography regarding signs of liver fibrosis; (3) histopathological findings in liver tissue of PMM2-CDG patients include cytoplasmic glycogen deposits; and (4) most CDG types show more than one type of liver injury. Conclusions Based on these findings, we recommend that all CDG patients have regular systematic, comprehensive screening for liver disease, including physical examination (for hepatomegaly and signs of liver failure), laboratory tests (serum alanine aminotransferase and aspartate aminotransferase), liver ultrasound (for steatosis and liver tumors), and liver elastography (for fibrosis).

One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.

No abstract