D-Glyceric Acidemia: An Inborn Error Associated with Fructose Metabolism

Abstract

ABSTRACT. A mentally retarded girl with epileptic sei-CASE REPORT zures is described. urinary organic acid screening ievealed a massive excretion of glyceric acid, a normally barely detectable metabolite. Hyperglycinemia was not observed. Capillary gas chromatography of the 0-acetylated (-)-menthyl ester of urinary glyceric acid showed the substance to have the D-configuration. The urinary D-glycerate excretion remained unaltered after an oral load with 200 mg/kg L-serine, but oral loading with fructose (1 g/kg) or dihydroxyacetone (1 g/kg) caused a sharp increase of the Dglycerate excretion. Treatment with a diet moderately restricted in fructose led to some clinical improvement as judged by subjective criteria. The metabolic lesion is thought to be located at some step of the fructose catabolic pathway, possibly at the level of hepatic triokinase deficiency. (Pediatr Res 21: 502-506, 1987) Abbreviations GAPD, glyceraldehyde-3-phosphate dehydrogenase NKH, nonketotic hyperglycinemia TMS, trimethylsilyl Hb, hemoglobin D-Glyceric acidemia seems to be an extremely rare inborn error of metabolism. To date only three isolated cases have been reported (1-3). The clinical presentation of the patients varied: the patient described by Wadman et al. (2) had a chronic metabolic acidosis and only a moderate developmental delay, whereas the patients described by Brandt et al. (I) and Grandgeorge et al. (3) showed all characteristic symptoms of NKH such as extreme hypotonia, deep mental retardation, myoclonic jerks, and grand ma1 seizures. Brandt's patient not only had the clinical signs of NKH, but actually had elevated levels of glycine in his plasma and urine. The concentration of D-glycerate in urine of the previously described patients ranged from 1-1 16 mmol/liter.A clear-cut enzyme defect leading to D-glyceric acidemia has not yet been found, although K$lvraa et al. (4) found evidence for a decreased activity of D-glycerate dehydrogenase in the fresh leukocytes of Brandt's patient. Enzyme studies were not performed in the other two patients.Herein we describe a patient with ~-glyceric acidemia. Results of biochemical investigations as well as of clinical studies, designed to obtain more insight in the metabolic defect, will be given.Received June 2, 1986; accepted December 19, 1986. Correspondence Dr. M. Duran, University Children's Hospital, Het Wilhelmina Kinderziekenhuis, Nieuwe Gracht 137, 3512 LK Utrecht, The Netherlands.The proband B., the first child of healthy, nonrelated parents, was born at home after an uneventful gestation of 38 wk; her birth weight was 2800 g. There were signs of perinatal asphyxia: crying started late. Apgar scores were not recorded. The mother's next pregnancy ended with a spontaneous abortion at 1 1 wk; the third pregnancy resulted in the birth of a child with spina bifida who died in the neonatal period. Subsequently two healthy children were born.In the first weeks of life the patient was noted to be hypotonic and she had severe feeding difficulties. Motor development was slo...

D‐Glycerate kinase deficiency as a cause of D‐glyceric aciduria

“…In contrast, D-glycerate overproduction might be the cause of the D-glyceric aciduria in the patient described by Duran et al [4]. The excretion of D-glyceric acid by this patient was extremely dependent on the ingestion of fructose or of dihydroxyacetone, and was not influenced by a serine load.…”

Pitfalls in the diagnosis of glycine encephalopathy (non‐ketotic hyperglycinemia)

“…1 Only a handful of cases of D-glyceric aciduria have been reported, [47][48][49][50][51][52][53] one of which was in an Afghan hound. 53 The underlying defect is unclear, but deficiencies of D-glycerate dehydrogenase, 54 triokinase, 50 or D-glycerate kinase 52,55 have been proposed. Clinical features in these cases have included severe neurological impairment and persistent metabolic acidosis.…”

Chiral liquid chromatography tandem mass spectrometry in the determination of the configuration of glyceric acid in urine of patients with D‐glyceric and L‐glyceric acidurias

“…In 1976, a second patient was studied of an Afghani origin, excreting excess D-glyceric acid, normal glycine with a different clinical picture of tachypnea, tachycardia, metabolic acidosis and neurologically normal (Wadman et al, 1976). After these two cases had been described, several other cases came to light and the enzyme deficiency has been determined to be D-glycerate kinase, the enzyme involved in the conversion of D-glyceric to D-2-phosphoglycerate (Kølvraa et al, 1984;Duran et al, 1987;Fontaine et al, 1989;Van Schaftingen, 1989;Bonham et al, 1990).…”