Antenatal diagnosis of argininosuccinic aciduria

Abstract

Argininosuccinic aciduria (ASAuria) is an inherited disorder of ureogensis characterized by periodic hyperammonemia, seizures, and mental retardation. Transabdominal amniocentesis was performed at 16 weeks' gestation on a 31‐year‐old female whose one previous child had this disease. ASA concentration in the amniotic fluid was 0.073 μmoles/ml (normal = 0). Cultured amniotic cells incubated with L‐citrulline‐ureido‐ 11 C accumulated ASA‐ 14 C as did cultured fibroblasts of patients with ASAuria; normal cells (including those from subjects heterozygous for argininosuc‐cinasc deficiency) do not accumulate this metabolic intermediate. Pregnancy was terminated at 22 weeks by hysterotomy. Fetal liver ASase was 3–5 percent of normal, and liver ASA concentration was 9.36 μmoles/g wet wt. (normal = 0), confirming the prediction of an affected fetus. Fetal cord serum ASA and citrulline concentrations were 0.098 and 0.071 μmoles/ml, respectively; simultaneous maternal concentrations were 0 and 0.014. Maternal urine ASA concentrations during pregnancy were 0.15.5 and 0.166 μmoles/mg crmtinine; 10 weeks after tcrmination, ASA was present in only trace amounts. Current emphasis is on development of techniques to minimize the delay between amniocentesis and intrauterine diagnosis. It is possible that this and some other no‐threshold aminoacidurias may be diagnosed on the basis of amniotic fluid amino acids alone.