PMM2-CDG and nephrotic syndrome: a case report.

CDG are a group of diseases altering the glycosylation process. Enzymes involved have ubiquitous distribution with systemic involvement and high phenotypic variability. We report the case of a girl with central hypotonia, epilepsy and severe psychomotor delay diagnosed with phosphomannomutase 2 deficiency (PMM2-CDG) after presenting with nephrotic syndrome.

Mannose supplementation in PMM2-CDG

In this response to the letter by Witters et al., we refer to the authors' arguments regarding spontaneous enhancement of glycosylation and the claim, that mannose has no place in the treatment of PMM2-CDG. Our paper “Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)” has shown that further investigation of mannose in PMM2-CDG is worthwhile alongside other treatment options and should not be dismissed off-hand without the willingness to prove or disprove it in controlled prospective clinical trials.

Enzymatic Production of β-Glucose 1,6-Bisphosphate Through Manipulation of Catalytic Magnesium Coordination

<p>Manipulation of enzyme behaviour represents a sustainable technology that can be harnessed to enhance the production of valuable metabolites and chemical precursors. b-glucose 1,6-bisphosphate (bG16BP) is a native reaction intermediate in the catalytic cycle of b-phosphoglucomutase (bPGM) that has been proposed as a treatment for human congenital disorder of glycosylation involving phosphomannomutase 2 (PMM2). Studies of both bPGM and PMM2 could benefit from a green and high-yielding method for bG16BP production. Three strategies have been reported previously for the synthesis of bG16BP; however, each of these methods either delivers low yields or uses chemicals and procedures with significant environmental impacts. Herein, through combined use of NMR spectroscopy, kinetic assays and site-directed mutagenesis, we report the efficient enzymatic synthesis of anomer-specific bG16BP using a variant of bPGM. Further purification, employing a simple environmentally considerate precipitation procedure requiring only a standard biochemical toolset, results in a product with high purity and yield. Moreover, this synthesis strategy illustrates how manipulation of the catalytic magnesium coordination of an enzyme can be utilised to generate large quantities of a valuable metabolite.</p>

Enzymatic Production of β-Glucose 1,6-Bisphosphate Through Manipulation of Catalytic Magnesium Coordination

<p>Manipulation of enzyme behaviour represents a sustainable technology that can be harnessed to enhance the production of valuable metabolites and chemical precursors. b-glucose 1,6-bisphosphate (bG16BP) is a native reaction intermediate in the catalytic cycle of b-phosphoglucomutase (bPGM) that has been proposed as a treatment for human congenital disorder of glycosylation involving phosphomannomutase 2 (PMM2). Studies of both bPGM and PMM2 could benefit from a green and high-yielding method for bG16BP production. Three strategies have been reported previously for the synthesis of bG16BP; however, each of these methods either delivers low yields or uses chemicals and procedures with significant environmental impacts. Herein, through combined use of NMR spectroscopy, kinetic assays and site-directed mutagenesis, we report the efficient enzymatic synthesis of anomer-specific bG16BP using a variant of bPGM. Further purification, employing a simple environmentally considerate precipitation procedure requiring only a standard biochemical toolset, results in a product with high purity and yield. Moreover, this synthesis strategy illustrates how manipulation of the catalytic magnesium coordination of an enzyme can be utilised to generate large quantities of a valuable metabolite.</p>

Enzymatic Production of β-Glucose 1,6-Bisphosphate Through Manipulation of Catalytic Magnesium Coordination

<p>Manipulation of enzyme behaviour represents a sustainable technology that can be harnessed to enhance the production of valuable metabolites and chemical precursors. b-glucose 1,6-bisphosphate (bG16BP) is a native reaction intermediate in the catalytic cycle of b-phosphoglucomutase (bPGM) that has been proposed as a treatment for human congenital disorder of glycosylation involving phosphomannomutase 2 (PMM2). Studies of both bPGM and PMM2 could benefit from a green and high-yielding method for bG16BP production. Three strategies have been reported previously for the synthesis of bG16BP; however, each of these methods either delivers low yields or uses chemicals and procedures with significant environmental impacts. Herein, through combined use of NMR spectroscopy, kinetic assays and site-directed mutagenesis, we report the efficient enzymatic synthesis of anomer-specific bG16BP using a variant of bPGM. Further purification, employing a simple environmentally considerate precipitation procedure requiring only a standard biochemical toolset, results in a product with high purity and yield. Moreover, this synthesis strategy illustrates how manipulation of the catalytic magnesium coordination of an enzyme can be utilised to generate large quantities of a valuable metabolite.</p>