PROSPECTIVE DIAGNOSIS AND TREATMENT OF UREA CYCLE DISORDERS

Abstract

Of 31 infants known to be at risk for a urea cycle defect because of family history, 18 were treated prospectively from birth with a disease-specific diagnostic and therapeutic protocol. Diagnosis was made on the basis of plasma citrulline and ASA levels over the first 72 hrs of life. Of the 7 affected infants in the prospectively treated group (OTC-3; CPS-1 AS-2; AL-1), one OTCD infant died (peak NH₄ 850uM) and 6 survived the neonatal period .(peak NH₄ 52-197uM). One OTCD survivor died at 33mos; 5 remain on therapy (ages 18-60mos). Developmental quotients for survivors range from 55-101. 16 prospectively-treated unaffected infants are normal at 9-60mos and show no ill effects from 4 days of therapy. In addition, 7 affected infants (OTC-4; CPS-2.; AS-1) were managed outside the protocol with observation, protein-restriction and/or IV benzoate and arginine and peritoneal dialysis after the onset of symptomatic hyperammonemia. Diagnosis was made 25-90hrs after birth. All 4 OTCD infants expired (2 were untreated). The 3 survivors are now 18-48 mos and remain on therapy. Peak neonatal ammonium levels ranged from 210-364uM. DQ scores in the CPSD patients are 99 and 133, while the ASD patient has a score of 55.

We conclude: 1) assessment of plasma citrulline and ASA levels reliably identify affected infants within 72 hrs of birth; 2) the prevention of neonatal hyperammonemia by prospective therapy improves survival; and 3) neurologic outcome is improved with early therapy in infants at risk for OTCD, CPSD, and ASD.

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