Inborn error of metabolism resulting in d-glyceric acidemia, developmental delay, and seizures.
d-Glycerate Kinase Deficiency.
Extremely rare disorder (fewer
than 10 cases have been reported) with autosomal recessive transmission.
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.
No references to anesthesia were found.
However, the presence of severe acidemia, seizures, and developmental delay
are considerations individually associated with their manifestations.
Anticonvulsant medication should be continued.
Duran M, Beemer FA, Bruinvis L, et al: d
-Glyceric acidemia: An
inborn error associated with fructose metabolism. Pediatr Res
Kolvraa S, Christensen E, Brandt NJ: Studies of the glycine metabolism in a
patient with d
-glyceric acidemia and hyperglycinemia. Pediatr Res
Kolvraa S, Rasmussen K, Brandt NJ: d
-Glyceric acidemia: Biochemical
studies of a new syndrome. Pediatr Res