title: Pregnancy in a healthy woman with untreated citrullinemia.
abstract: We report the clinical and biochemical data on a second successful pregnancy in a woman with citrullinemia due to argininosuccinate synthetase deficiency (CTLN1). Despite very elevated plasma and urine citrulline and little or no measurable argininosuccinate synthetase enzyme activity on cultured skin fibroblasts, this 29-year-old woman, who was identified through newborn screening, has remained asymptomatic throughout her life. Mutation analysis has recently revealed that she is a compound heterozygote for a known and a novel mutation (IVS15-1G > C and K310Q, respectively). Many newborn screening programs have recently been expanded to include citrullinemia and numerous asymptomatic hypercitrullinemic infants and children have been identified. It is now important to define prognostic indicators that will help with treatment decisions and genetic counseling for these patients. This patient, as the only citrullinemic adult who has been followed prospectively, contributes important information in this regard. In addition, her child was unaffected by the high citrulline levels demonstrated in amniotic fluid and breast milk suggesting that citrulline is not teratogenic. Although pregnancy is an important risk factor for women with CTLN1, it appears that females with citrullinemia can have normal pregnancy outcomes, as long as metabolic crisis is avoided.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. mpotter@hhsc.ca
authors.forename: Murray A
authors.initials: MA
authors.lastname: Potter
authors.forename: Susan
authors.initials: S
authors.lastname: Zeesman
authors.forename: Barbara
authors.initials: B
authors.lastname: Brennan
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Gao
authors.forename: Ayako
authors.initials: A
authors.lastname: Tabata
authors.forename: Takeyori
authors.initials: T
authors.lastname: Saheki
authors.forename: Donald T
authors.initials: DT
authors.lastname: Whelan
mesh_terms: D000328:Adult; D001124:Argininosuccinate Synthase / Q000235:genetics / Q000378:metabolism; D002956:Citrulline / Q000097:blood / Q000652:urine; D020159:Citrullinemia / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome
chemical_list: D002956:Citrulline; D001124:Argininosuccinate Synthase