Nonketotic hyperglycinemia

Baumgartner, R.; Ando, Toshiyuki; Nyhan, William L.

doi:10.1016/s0022-3476(69)80341-0

Cited by 61 publications

(40 citation statements)

References 15 publications

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“…Curves representing patients KH and CE were rather flat, rising slowly to maximum specific activities at 30-60 min and then gradually declining; in contrast, curves for control subjects declined rapidly from peak levels at 10-20 min. The curves for KH and CE were indistinguishable from those for RH, TZ, and SF, the latter being patients with nonketotic hyperglycinemia who have a defect in the conversion of the first carbon of glycine to CO 2 [2,5]. In VB, the defect was much less prominent except at the earliest time point, after which specific activity rose so that by 60 min the values for this patient could not be distinguished from those for control subjects.…”

Section: The Oxidation Of Glycine In Vivomentioning

confidence: 75%

“…MK, JE, and MS were control subjects. SF, RH, and TZ were patients with nonketotic hyperglycinemia [2,5]. The designation +G indicates the creation of a large glycine pool in a control subject by continuous infusion of nonisotopic glycine.…”

Section: Studies Of the Oxidation Of Propionate In Vitromentioning

confidence: 99%

“…The line was fitted manually. Data on control subjects JE, MK, and MS and on patients with nonketotic hyperglycinemia TZ, RH, and SF have previously been reported [2,5]. KH was a patient with ketotic hyperglycinemia.…”

Section: The Oxidation Of Glycine In Vivomentioning

confidence: 99%

“…Expired air was collected at intervals, its CO 2 was trapped in ethanolamine, and its isotope and CO 2 content were determined. Control data on glycine metabolism have been published [2,5]. Control subjects for the study of propionate metabolism were a patient, LG, with B 12 -independent methylmalonic acidemia [15]; a patient, DG, with cerebral gigantism [6]; and a patient, AMc, with the Cornelia de Lange syndrome.…”

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confidence: 99%

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The Oxidation of Glycine and Propionic Acid in Propionic Acidemia with Ketotic Hyperglycinemia

et al. 1972

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ExtractKetotic hyperglycinemia is a syndrome in which elevated concentrations of glycine occur in body fluids of patients who manifest life-threatening episodes of ketoacidosis very early in life. The disorder originally described under this heading is now known to be more reliably categorized by propionic acidemia than by hyperglycinemia. Studies of the metabolism of glycine and of propionate in this condition have been undertaken. Conversion of glycine-1-14 C and of propionate-1-U C to 14 CO 2 has been studied both in vivo and in vitro. Conversion of glycine-2-14 C to serine-3-14 C has been studied in vivo. It was found that the conversion of glycine-1-14 C to CO 2 in vivo was defective in all three of the patients with ketotic hyperglycinemia. At the earliest time points, the specific activities of expired CO 2 in control subjects varied from 25 to more than 60 dpm/jumole, whereas in patients these values did not exceed 10 and were less than 5 in two patients. Conversion of the second carbon of glycine to the third carbon of serine was normal. The relative specific activity of the third carbon was 20. This value was 2-10 times the values found previously in patients with nonketotic hyperglycinemia where this conversion is defective. Conversion of propionate-1-14 C to CO 2 was defective both in vivo and in vitro in patients with ketotic hyperglycinemia and with methylmalonic acidemia. In control subjects, specific activities of the CO 2 expired following injection of propionate-1-14 C approximated 200 dpm/^mole at the earliest time points, whereas in VB the comparable specific activity was close to 0. Activity of propionylcoenzyme A (CoA) carboxylase was absent in the fibroblasts of a patient with ketotic hyperglycinemia. Values of 15-30 dpm/5 mg protein obtained in the patient do not seem to differ significantly from 0, whereas in control subjects the values ranged from 985 to 2655 dpm/5 mg protein. These observations indicate that there are defects in the metabolism of both glycine and propionate in patients with ketotic hyperglycinemia. Speculation

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Section: The Oxidation Of Glycine In Vivomentioning

confidence: 75%

Section: Studies Of the Oxidation Of Propionate In Vitromentioning

confidence: 99%

Section: The Oxidation Of Glycine In Vivomentioning

confidence: 99%

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confidence: 99%

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The Oxidation of Glycine and Propionic Acid in Propionic Acidemia with Ketotic Hyperglycinemia

et al. 1972

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“…[1][2][3] Absence of metabolic acidosis serves to distinguish it from the ketotic type, in which hyperglycinemia is secondary to certain organic acidemias such as ß-ketothiolase deficiency, propionic, methylmalonic and isovaleric acidemias. 4,5 NKH is a wellrecognized metabolic cause of life-threatening illness in the neonate that presents with poor feeding and decreased activity, with or without seizures. This usually progresses to apnea, coma and death.…”

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confidence: 99%

Nonketotic Hyperglycinemia: A Life-Threatening Disorder in Saudi Newborns

et al. 1996

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Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder due to a fundamental defect in the glycine cleavage system, which leads to neuronal dysfunction caused by two receptor-mediated mechanisms. It is a lifethreatening condition in the neonate. Until now, the disease has not been described from Saudi Arabia. We report on three Saudi newborns (two males and one female) who had NKH. Two of these were siblings (male and female). Following uneventful deliveries, they presented between the first and third day of life with progressive lethargy, poor feeding, recurrent apnea and severe hypotonia. Two newborns had myoclonic seizures, whereas electroencephalogram showed burst-suppression pattern in all of them. The diagnosis was confirmed by high cerebrospinal fluid/plasma glycine ratio (0.2 and 1.08) in two patients (normal < 0.03), whereas a sibling of one of the neonates had a high glycine level. Both siblings died during the second month of life despite therapy with dextromethorphan (an N-methyl-D-aspartate [NMDA] receptor antagonist) in one of them. The third baby had ketamine (noncompetitive NMDA receptor antagonist) and sodium benzoate (that conjugates with glycine, forming nontoxic hippuric acid). Although his seizures were controlled, he survived with severe neurological sequelae. Ann Saudi Med 1996;16(4): [400][401][402][403][404]. Nonketotic hyperglycinemia (NKH) is an inherited autosomal recessive inborn error of the glycine cleavage system resulting in the presence of a high glycine level (Figure 1) in the body fluids.1-3 Absence of metabolic acidosis serves to distinguish it from the ketotic type, in which hyperglycinemia is secondary to certain organic acidemias such as ß-ketothiolase deficiency, propionic, methylmalonic and isovaleric acidemias.4,5 NKH is a wellrecognized metabolic cause of life-threatening illness in the neonate that presents with poor feeding and decreased activity, with or without seizures. This usually progresses to apnea, coma and death. Those who survive are severely handicapped.6 A late-onset form has also been described in which patients develop neurological symptoms of varying degrees after the neonatal period. 7The pathophysiologic effects of hyperglycinemia were attributed to the resulting neuronal dysfunction caused by two receptor-mediated mechanisms. These are the inhibitory effects of glycine at the postsynaptic strychninesensitive receptor, 8,9 and overstimulation of the excitatory glycine receptor, which is linked to, and allosterically activates, the N-methyl-D-aspartate (NMDA) receptor. The latter is one of the major subtypes of excitatory amino acid receptors in the brain. Attempts at treating NKH have included the administration of benzoate to conjugate the glycine forming nontoxic hippuric acid.11 Ketamine, a noncompetitive NMDA receptor antagonist, was also tried and found to improve seizure frequency on the electroencephalogram (EEG). 12 Another noncompetitive antagonist at the NMDA receptor is dextromethorphan. This also had documented beneficial ef...

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Benzoate therapy and carnitine deficiency in non‐ketotic hyperglycinemia

et al. 1995

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Five patients presenting with non-ketotic hyperglycinemia in the neonatal period were treated with sodium benzoate to normalize plasma glycine levels. This therapy resulted in seizure reduction and a marked increase in wakefulness. Plasma carnitine deficiency was noted in three of four patients tested, and benzoylcarnitine was identified in plasma, urine, and CSF. Treatment with L-carnitine normalized plasma free carnitine. L-carnitine showed a tendency to increase the glycine conjugation of benzoate. An episode of coma and increased seizures in one patient was associated with a toxic level of benzoate, probably due to insufficient mobilization of glycine for conjugation. High dose benzoate therapy improved the quality of life of surviving patients. Close monitoring of glycine, benzoate and carnitine levels is advised.

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Nonketotic hyperglycinemia

Cited by 61 publications

References 15 publications

The Oxidation of Glycine and Propionic Acid in Propionic Acidemia with Ketotic Hyperglycinemia

The Oxidation of Glycine and Propionic Acid in Propionic Acidemia with Ketotic Hyperglycinemia

Nonketotic Hyperglycinemia: A Life-Threatening Disorder in Saudi Newborns

Benzoate therapy and carnitine deficiency in non‐ketotic hyperglycinemia

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