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At a glance

It is part of a group of inborn error of metabolism resulting in D-glyceric academia. The clinical features include a progressive encephalopathy, severe mental/psychomotor retardation, seizures, microcephaly, hypotonia, failure to thrive, severe metabolic acidosis, and early death in the full expressed disorder, whereas those affected with the mild phenotype have light speech delay or even normal development.

Synonym

D-Glycerate Kinase Deficiency; D-Glyceric Aciduria.

Incidence

Extremely rare disorder with fewer than 10 cases reported in the medical literature.

Genetic inheritance

An autosomal recessive transmission with a highly variable phenotype. It is caused by a mutation in the gene GLYCTK, which encodes for the enzyme glycerate kinase.

Pathophysiology

The enzyme glycerate kinase catalyses the enzymatic conversion of D-glyceric acid to 2-phosphoglycerate. This enzymatic conversion is an intermediary reaction found in several metabolic pathways, particularly in the breakdown of fructose.

Diagnosis

A deficiency in glycerate kinase activity leads to the accumulation of D-glyceric acid in bodily fluids and tissues. The diagnosis is established by measuring the level of organic acids in the plasma and urine of affected individuals after a glucose intake challenge.

Clinical aspects

Initially described case of a mentally retarded boy of nonconsanguineous Serbian parents suffered clinically from nonketotic hyperglycinemia. Extremely high concentrations of D-glyceric acid were found in both serum and urine. Enzyme assays of D-glyceric dehydrogenase (glyoxylate reductase) on blood leukocytes demonstrated significantly lower activity in the patient compared to five normal children. Further measurements of glycine cleavage activity in autopsic liver tissue from this patient revealed only 10% of normal activity. The two compounds, 2-methylbutyryl-CoA and isobutyryl-CoA, are known inhibitors of the glycine cleavage system. Based on the findings of increased urinary excretion of both free and conjugated isobutyric acid, 2-methylbutyric acid, and isovaleric acid, it was hypothesized that decreased glycine cleavage activity might be a result of inhibition by these three substances. However, in the liver of another patient with this disease, glycerate kinase activity was less than 5% of normal, and D-glycerate dehydrogenase and triokinase activities were not deficient. Therefore, D-glycerate kinase deficiency was suggested to be the cause of D-glyceric aciduria. However, a primary defect in the catabolism of L-serine catabolism cannot be excluded. An oral fructose loading dose resulted in a sharp increase of D-glycerate excretion. Subjective clinical improvement was reported after a diet moderately restricted in fructose. Clinical symptoms of this disease are global developmental delay and seizures. Severe metabolic acidosis and failure to thrive are common and may require chronic therapy with bicarbonate.

Anesthetic considerations

No references to anesthesia were found. However, the presence of severe acidemia, seizures, and developmental delay ...

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