Clinical Outcomes of Neonatal Onset Proximal versus Distal Urea Cycle Disorders Do Not Differ

Objective To compare the clinical course and outcome of patients diagnosed with one of 4 neonatal-onset urea cycle disorders (UCDs): deficiency of carbamyl phosphate synthase 1 (CPSD), ornithine transcarbamylase (OTCD), argininosuccinate synthase (ASD), or argininosuccinate lyase (ALD). Study design Clinical, biochemical, and neuropsychological data from 103 subjects with neonatal-onset UCDs were derived from the Longitudinal Study of Urea Cycle Disorders, an observational protocol of the Urea Cycle Disorders Consortium, one of the Rare Disease Clinical Research Networks. Results Some 88% of the subjects presented clinically by age 7 days. Peak ammonia level was 963 mu M in patients with proximal UCDs (CPSD or OTCD), compared with 589 mu M in ASD and 573 mMin ALD. Roughly 25% of subjects with CPSD or OTCD, 18% of those with ASD, and 67% of those with ALD had a "honeymoon period," defined as the time interval from discharge from initial admission to subsequent admission for hyperammonemia, greater than 1 year. The proportion of patients with a poor outcome (IQ/Developmental Quotient <70) was greatest in ALD (68%), followed by ASD (54%) and CPSD/OTCD (47%). This trend was not significant, but was observed in both patients aged <4 years and those aged >= 4 years. Poor cognitive outcome was not correlated with peak ammonia level or duration of initial admission. Conclusion Neurocognitive outcomes do not differ between patients with proximal UCDs and those with distal UCDs. Factors other than hyperammonemia may contribute to poor neurocognitive outcome in the distal UCDs. (J Pediatr 2013;162:324-29).