The Treatment of Congenital Galactosaemia

Jones, Norman L.; Leak, David J.

doi:10.1136/adc.34.176.307

Cited by 9 publications

(3 citation statements)

References 12 publications

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“…The exact pathophysiology of these acute symptoms remains uncertain, partially because of the lack of experimental animal model for this disease (Leslie et al, 1996), but the accumulation of gal-1P is regarded as one of the most important pathogenic factors (Gitzelmann et al, 1967; Gitzelmann, 1995). The best treatment for Classic Galactosemia to-date is the removal of galactose from the patients’ diet to prevent the manifestation of the acute toxicity syndrome (Mason et al, 1935; Salt et al, 1955; Jones and Leak, 1959; Bosch, 2006). However, long-term complications such as IQ deficits, ataxia, speech dyspraxia, and premature ovarian insufficiency persist in many patients with a galactose-restricted diet (Waggoner et al, 1990; Waisbren et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Correlation assessment among clinical phenotypes, expression analysis and molecular modeling of 14 novel variations in the human galactose-1-phosphate uridylyltransferase gene

et al. 2012

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Galactose-1-phosphate uridylyltransferase (GALT) catalyses the conversion of galactose-1-phosphate to UDP-galactose, a key step in the galactose metabolism. Deficiency of GALT activity in humans caused by deleterious variations in the GALT gene can cause a potentially lethal disease called Classic Galactosemia. In this study, we selected 14 novel nucleotide sequence changes in the GALT genes found in galactosemic patients for expression analysis and molecular modeling. Several variants showed decreased levels of expression and decreased abundance in the soluble fraction of the Escherichia coli cell extracts, suggesting altered stability and solubility. Only six variant GALT enzymes had detectable enzymatic activities. Kinetic studies showed that their Vmax decreased significantly. To further characterize the variants at molecular level, we performed static and dynamic molecular modeling studies. Effects of variations on local and/or global structural features of the enzyme were anticipated for the majority of variants. In-depth studies with molecular dynamic simulations on selected variants predicted the alteration of the protein structure even when static models apparently did not highlight any perturbation. Overall, these studies offered new insights on the molecular properties of GALT enzyme, with the aim of correlating them with the clinical outcome.

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Section: Introductionmentioning

confidence: 99%

Correlation assessment among clinical phenotypes, expression analysis and molecular modeling of 14 novel variations in the human galactose-1-phosphate uridylyltransferase gene

et al. 2012

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“…Mason and Turner ( 1935 ) were the first to report the successful use of a milk-free diet in an infant with galactosemia. In the 1950s, different strategies to feed infants a diet without galactose were discussed in the literature (Salt et al 1955 ; Jones and Leak 1959 ). Nowadays, initiating the diet is much easier, as infant formulas with a very limited amount of galactose are widely available.…”

Section: Introductionmentioning

confidence: 99%

Classic galactosemia: dietary dilemmas

Bosch

2010

J of Inher Metab Disea

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“…When exposed to galactose from breast milk or infant formula, affected newborn infants develop life-threatening symptoms that quickly resolve once a galactose-restricted diet is initiated. A very strict life-long galactose-restricted diet is the only available treatment since CG was first reported in more detail (Jones and Leak 1959). Despite good dietary adherence, individuals are at risk for developing long-term complications including speech and language impairment and impaired cognitive abilities (Bosch 2006).…”

Section: Introductionmentioning

confidence: 99%