[Lactic acidosis and accumulation of glutamate in the blood of neonates following treatment with calcium levulinate for hypocalcaemia].
The data from 5 clinics concerning 8 infants, who had developed severe lactic acidosis and hyperglutamic acidaemia were reviewed. Blood-lactate levels were up to 15 mmol/l (reference level: < 2) and plasma-glutamate levels up to 1632 pmol/l (reference level: 14-78), and there was no concomitant hyperglutaminaemia (levels up to 1032 micromol/l (reference level: 333-809)). A positive correlation between the amount of calcium levulinate administered and the degree of hyperglutamic acidaemia was found. Replacement of the calcium levulinate by another calcium salt caused a reversal of the biochemical abnormalities of the patients. Two of the infants had a 22q11 microdeletion. This development of severe acidosis in infants who had been given a calcium supplement in the form of calcium levulinate may be related to genetic predisposition. The paradoxal hyperketonaemia and generalized aminoaciduria in 4 other patients suggested disturbed function ofthe mitochondrial respiratory chain. The hypothesis of the occurrence of an underlying defect of the mitochondrial respiratory chain was tested in the muscle tissue of one 22q11 patient, but this showed no abnormalities. Excessive accumulation of glutamate because of dysfunction ofglutamine synthetase, which forms glutamate from glutamine seems unlikely because of the relatively low values of plasma glutamate compared to the glutamine plasma levels. Calcium levulinate should no longer be used in neonates as it may lead to lactic acidosis.
Williams
M
M
Erasmus MC-Centrum, afd. Klinische Genetica, Rotterdam. m.williams@erasmusmc.nl
Huijmans
J G M
JG
Duran
M
M
de Klerk
J B C
JB
van Maldegem
B T
BT
Poll-The
B T
BT
D000140:Acidosis, Lactic / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000097:blood*; D006801:Humans; D006996:Hypocalcemia / Q000188:drug therapy*; D007231:Infant, Newborn; D007773:Lactates / Q000097:blood; D007982:Levulinic Acids / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male
D004791:Enzyme Inhibitors; D007773:Lactates; D007982:Levulinic Acids; D018698:Glutamic Acid; C032246:levulinic acid