Biochemical Medicine and Metabolic Biology
Characterization of a novel biochemical abnormality in galactosemia: Deficiency of glycolipids containing galactose or N-acetylgalactosamine and accumulation of precursors in brain and lymphocytes
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Cited by (68)
Gray and white matter are both affected in classical galactosemia: An explorative study on the association between neuroimaging and clinical outcome
2020, Molecular Genetics and MetabolismCitation Excerpt :As previous studies have suggested that myelin is affected in CG patients [2,5,14,15] we investigated R1 values indicative of myelin content. The formation of myelin depends on galactose containing glycolipids, such as galactocerebrosides [46,47] and the deficient GALT enzyme in CG patients causes a reduction in UDP-sugars which are essential for the formation of glycoproteins and glycolipids [8]. Therefore, the observed WM abnormalities on MRI in CG patients, such as the abnormal WM intensity signal, have been attributed to abnormal myelination.
Hereditary galactosemia
2018, Metabolism: Clinical and ExperimentalCitation Excerpt :UDP-hexose deficiency and/or imbalance have been pointed out as an important pathogenic mechanism [98–102]. Abnormal pattern of glycoproteins [53] and deficiency of glycolipids containing galactose or N-acetylgalactosamine [103] have been observed in postmortem galactosemic brain. Studies with patients' fibroblasts have described defective galactosylation [104,105].
Reversal of aberrant PI3K/Akt signaling by Salubrinal in a GalT-deficient mouse model
2017, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :The molecular mechanisms of these acute and long-term complications are still poorly understood despite several hypotheses that have been presented in the literature [7–11]. Among the biochemical abnormalities detected in patients, glycosylation defects of glycoproteins and glycolipids have received significant attention [8,12–15]. It has been suggested that the observed glycosylation defects are caused by the accumulation of toxic galactose metabolites of the blocked GALT reaction, as well as deficiency of UDP-galactose (Fig. 1) [15,16].
The molecular basis of galactosemia — Past, present and future
2016, GeneCitation Excerpt :In addition to decreased galactosylation, increased inappropriate incorporation of other monosaccharide moieties such as fucose has been observed (Sturiale et al., 2005). Similarly, glycolipids from galactosemic patients were shown to have reduced levels of galactose and N-acetylgalactosamine compared to healthy patients; this effect was not reversed by a low galactose diet (Petry et al., 1991). In galactosemic patients, N-linked protein glycosylation is associated with increased amounts of mannose and increased numbers of truncated oligosaccharide chains (Liu et al., 2012; Staubach et al., 2012).
Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism?
2014, Molecular Genetics and MetabolismCitation Excerpt :If galactose intoxication disrupts the localisation of ALG9, even to a minor degree, this in combination with decreased UDP-galactose levels, and the dysregulation of other glycosyltransferases, could have a significant role to play in systemic glycosylation defects. Severe galactose intoxication during the neonatal stage results in gross assembly defects in patients [8,12–15,59], which supports our findings here of a susceptibility of the assembly stage of glycosylation during exposure to galactose. The abnormal expression of ALG9 gene, and potential defects in protein level and localisation in cells, may be a marker for individuals at risk of aberrant glycosylation during increased galactose intake.
N- and O-linked glycosylation of total plasma glycoproteins in galactosemia
2012, Molecular Genetics and MetabolismCitation Excerpt :In the early 1970s, Haberland and colleagues [3,4] demonstrated an abnormal pattern of glycoproteins in the postmortem brain of a galactosemic patient. Twenty years later, Petry and colleagues [5] described a deficiency of glycolipids containing galactose or N-acetylgalactosamine, and an accumulation of the precursors of these moieties in the postmortem brain of a neonate with galactosemia. Also in the early 1990s, Jaeken and colleagues described abnormalities in the glycosylated serum lysosomal enzymes from patients with galactosemia [6], and Dobbie and colleagues [7] and Ornstein and colleagues [8] reported defective galactosylation of complex carbohydrates and glycoproteins in fibroblasts derived from patients with galactosemia.
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Present address: Université de Bordeaux II, Department d' Immunologie et de Biologie Parasitaire, F-33076 Bordeaux, France.