title: High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations.
abstract: Type 1 citrullinemia (CTLN1) often presents as a hyperammonemic encephalopathy in the neonatal period, but it can also develop in the late-infantile period and in adults. In addition, some patients can be identified in the presymptomatic period by neonatal or family member screening. In this study, twenty Korean patients with CTLN1 (19 families) were examined; fourteen patients with neonatal-onset, three with late-onset, and three that were identified presymptomatically. The 13 patients with hyperammonemic encephalopathy received continuous venovenous hemofiltration (CVVH) or peritoneal dialysis (PD). Although the hyperammonemia was relieved more effectively in the six patients on CVVH than the seven on PD, most of these patients suffered from severe neurologic deficits. Recurrent hyperammonemic episodes (7 pts, 35%), recurrent and reversible acute hepatic dysfunction (5 pts, 25%), and focal cerebral infarction (2 pts, 10%) were noted. The neonates with hyperammonemic encephalopathy had extensive brain injuries at the onset of hyperammonemia, followed by encephalomalacia and brain atrophy at quite an early age. Genetic testing for the ASS1 gene revealed a different mutation spectrum from those of other ethnicities; Three common mutations, c.421-2A>G (37.8%), c.1128-6_1188dup67 (18.9%), and p.Gly324Ser (16.2%), accounted for 73% of the mutations. The poor outcome was expected in patients with the peak ammonia level at onset over 600μmol/L, whose proportion was higher in the neonatal presentation group than in the presymptomatic/late presentation group. Our findings add to the current understanding of the ethnic diversity of CTLN1 from both clinical and genetic perspectives.
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Beom Hee
authors.initials: BH
authors.lastname: Lee
authors.forename: Yoo-Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Heo
authors.forename: Gu-Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Choi
authors.forename: Byong Sop
authors.initials: BS
authors.lastname: Lee
authors.forename: Ellen Ai-Rhan
authors.initials: EA
authors.lastname: Kim
authors.forename: Ki-Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Won Kyoung
authors.initials: WK
authors.lastname: Jhang
authors.forename: Seong Jong
authors.initials: SJ
authors.lastname: Park
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
mesh_terms: D001921:Brain / Q000473:pathology; D020159:Citrullinemia / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D015995:Prevalence; D056910:Republic of Korea / Q000453:epidemiology