Citrullinaemia type I: a common mutation in the Pacific Island population.
OBJECTIVE
The aim of this study was to develop and apply a mutation screening protocol for the ASS1 gene in order to confirm the diagnosis of citrullinaemia type I in neonates with elevated citrulline on expanded newborn screening (E-NBS).


METHODS
Three patients with an elevated citrulline level were identified via routine E-NBS between January and October 2008. Analysis of the ASS1 gene using a polymerase chain reaction and sequencing-based method was successfully applied to all three patients, together with a rapid mutation-specific detection method. Their clinical progress was followed for 16-22 months.


RESULTS
All three patients were homozygous for a previously reported missense mutation, c.787G>A (p.Val263Met), associated with a mild or asymptomatic clinical course.


CONCLUSIONS
As a consequence of E-NBS, an increasing number of neonates with elevated citrulline of uncertain clinical significance are being identified. Rapid sequence analysis of the ASS1 gene can be used to confirm citrullinaemia type I and, increasingly, to infer phenotypic severity. Homozygosity for the same mutation was found in all three patients despite non-consanguinity and variable Pacific Island origin. These data suggest that this mutation may be relatively prevalent in these ethnic groups and imply a possible founder effect.
Paediatric Metabolic Service, Starship Children's Hospital, Auckland, New Zealand.
Emma
E
Glamuzina
Renate
R
Marquis-Nicholson
Detlef
D
Knoll
Donald R
DR
Love
Callum
C
Wilson
D001124:Argininosuccinate Synthase / Q000235:genetics / Q000302:isolation & purification; D002956:Citrulline / Q000097:blood; D020159:Citrullinemia / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D018703:Founder Effect; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D010139:Pacific Islands
D002956:Citrulline; D001124:Argininosuccinate Synthase