Moderate citrullinaemia without hyperammonaemia in a child with mutated and deficient argininosuccinate synthetase.
In a patient with microcephaly, feeding problems and restlessness, moderately increased serum and urine citrulline concentrations were observed. Protein and allopurinol loading did not result in additional indications for a urea cycle defect. The diagnosis of citrullinaemia was made at both the enzyme and DNA level, resulting from a novel mutation in the argininosuccinate synthetase gene. The fact that the patient has not suffered from severe deterioration, and that there were only minor abnormalities in metabolite concentrations, suggests that the argininosuccinate synthetase capacity was less affected in vivo than in vitro. In vitro nuclear magnetic resonance investigation suggested an active acetylation mechanism for citrulline. This case illustrates the importance of performing extensive biochemical and molecular investigations in order to reach a definitive diagnosis, particularly in instances of moderate citrullinaemia.
Ruitenbeek
Wim
W
Laboratory of Pediatrics & Neurology, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. W.Ruitenbeek@cukz.umcn.nl
Kobayashi
Keiko
K
Iijima
Mikio
M
Smeitink
Jan A M
JA
Engelke
Udo F H
UF
De Abreu
Ronney A
RA
Kwast
Hanneke T
HT
Saheki
Takeyori
T
Boelen
Carolien A
CA
De Jong
Jan G N
JG
Wevers
Ron A
RA
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001124:Argininosuccinate Synthase / Q000172:deficiency* / Q000235:genetics*; D002675:Child, Preschool; D020159:Citrullinemia / Q000175:diagnosis*; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000175:diagnosis; D051379:Mice; D020125:Mutation, Missense; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism
D000596:Amino Acids; D001124:Argininosuccinate Synthase