SLC35A2-CDG is an X-linked congenital disorder of glycosylation (CDG), characterized by defective UDP-galactose transport into the Golgi and endoplasmic reticulum and consequent insufficient galactosylation of glycans. Clinically, this translates into a range of predominantly neurological symptoms. Although the pathomechanism of this disorder is not fully understood, oral galactose supplementation has led to clinical and biochemical improvement in some patients. Here, we show that protein glycosylation (N- and O-linked) was only minimally disturbed in SLC35A2-CDG patient-derived fibroblasts. However, lipid glycosylation was significantly impaired, with accumulation of glucosylceramide and deficiency of digalactosylated glycosphingolipids (GSLs) and complex gangliosides. Galactose supplementation increased UDP-galactose, its transport into the Golgi, and improved deficient GSL synthesis through direct incorporation of the provided galactose. This improved GSL homeostasis in all patient-derived fibroblasts and in another SLC35A2 deficient cell model (CHO-Lec8). Additionally, SLC35A2-CDG serum analysis identified hydroxylated GSLs, particularly GM3, as potential disease biomarkers. Given the essential role of gangliosides in central nervous system function, their deficiency is likely a key factor in the neurological involvement of this disorder. These findings pave the way for new nutritional therapies with GSL supplements and highlight the importance of studying lipid glycosylation to better understand the complex pathophysiology of CDG.

• Klíčová slova
• CDG, GSL, Gangliosides, Glycosphingolipids, SLC35A2-CDG, Tracer metabolomics,
• MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• fibroblasty metabolismus   účinky léků   MeSH
• galaktosa * farmakologie   metabolismus   MeSH
• glykosfingolipidy * biosyntéza   metabolismus   MeSH
• glykosylace účinky léků   MeSH
• Golgiho aparát metabolismus   MeSH
• lidé MeSH
• potravní doplňky MeSH
• proteiny přenášející monosacharidy MeSH
• vrozené poruchy glykosylace * metabolismus   patologie   genetika   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• galaktosa * MeSH
• glykosfingolipidy * MeSH
• proteiny přenášející monosacharidy MeSH
• UDP-galactose translocator MeSH Prohlížeč

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.

• Klíčová slova
• d-galactose, PGM1-CDG, congenital disorder of glycosylation, management guidelines, phosphoglucomutase 1 deficiency,
• MeSH
• dospělí MeSH
• galaktosa terapeutické užití   MeSH
• glykogenóza komplikace   diagnóza   farmakoterapie   enzymologie   MeSH
• hypoglykemie komplikace   MeSH
• kardiomyopatie komplikace   patologie   MeSH
• kojenec MeSH
• konsensus MeSH
• lidé MeSH
• management nemoci * MeSH
• mezinárodní spolupráce MeSH
• nemoci svalů komplikace   patologie   MeSH
• rozštěp patra komplikace   patologie   MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• směrnice pro lékařskou praxi MeSH
• Názvy látek
• galaktosa MeSH