Long-term outcome of patients with urea cycle disorders and the question of neonatal screening

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Abstract
With regard to the principles established for neonatal population screening, the question arises whether for patients with urea cycle disorders there is an accepted treatment which really affects the disease course and prognosis as compared to the natural history of these diseases. A retrospective study of 88 patients was performed. Based on questionnaires, the survival rate and neurodevelopmental outcome of patients treated with protein restriction alone was compared to the new therapy introduced in the 1980s with added citrulline/arginine, essential amino acids for improving the amino acid composition of the restricted natural protein and benzoate. Survival of patients with neonatal presentation was improved by the extensive therapy but this mostly at the cost of an increasing number of retarded patients. Long-term outcome did not differ significantly between the two treatments. Of all patients, 56% were symptomatic within 4 days of age and 67% within the 1st week. Thus a prevention of irreversible damage by neonatal screening on blood obtained at 3–4 days of life is questionable. Whether the benefit of obtaining a rapid diagnosis, e.g. for allowing proper counselling and prospective treatment, is acceptable for the parents of prospective patients remains open. The organisation of a dense network of specialised metabolic centres with sufficient staff and resources is a prior condition for any screening programme in order to ensure the rapid diagnosis, follow-up of treatment and counselling of a cumulative number of affected chronic patients needing this support. A commitment on a long-term basis by the institutions is needed in view of the health budget restrictions. Conclusion: in the short term, the goal is to detect hyperammonaemic patients as early as possible with special emphasis on sick neonates. In practice, quantitative plasma ammonia determination without delay is recommended in any newborn for whom a sepsis work-up is considered and in children who refuse feeding or vomit and show alterations of consciousness and/or neurological symptoms.