Advertisement

European Journal of Pediatrics

, Volume 162, Supplement 1, pp S29–S33 | Cite as

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

  • Claude Bachmann
Article

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.

Keywords

Hyperammonaemia Inborn errors of metabolism Neonatal screening Outcome Urea cycle disorders 

Abbreviations

PKU

phenylketonuria

UCD

urea cycle disorder

References

  1. 1.
    Bachmann C (1990) Urea cycle disorders. In: Fernandes J, Saudubray J, Tada K (eds) Inborn metabolic diseases: diagnosis and treatment. Springer, Berlin Heidelberg New York, pp 211–228Google Scholar
  2. 2.
    Bachmann C (2003) Outcome and survival of 88 patients with urea cycle disorders: a retrospective evaluation. Eur J Pediatr 162: 410–416PubMedGoogle Scholar
  3. 3.
    Bearn AG, Cusworth DC, Dean G, Frézal JP, Neifakh SA, Scheinberg IH, Scriver CR, Szeinberg A (1968) Screening for inborn errors of metabolism. WHO Tech Rep Ser 401: 1–57Google Scholar
  4. 4.
    Bickel H, Bachmann C, Beckers R, Brandt NJ, Clayton BE, Corrado G, Feingold HJ, Giardini O, Hammersen G, Schoenberg D (1981) Neonatal mass screening for metabolic disorders. Eur J Pediatr 137: 133–139Google Scholar
  5. 5.
    Brusilow SW, Horwich AL (2001) Urea cycle enzymes. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease, vol II. McGraw-Hill, New York, pp 1909–1963Google Scholar
  6. 6.
    Maestri NE, Hauser ER, Bartholomew D, Brusilow SW (1991) Prospective treatment of urea cycle disorders. J Pediatr 119: 923–928PubMedGoogle Scholar
  7. 7.
    Maestri NE, Clissold DB, Brusilow SW (1995) Long-term survival of patients with argininosuccinate synthetase deficiency. J Pediatr 127: 929–935PubMedGoogle Scholar
  8. 8.
    Maestri NE, Brusilow SW, Clissold DB, Bassett SS (1996) Long-term treatment of girls with ornithine transcarbamylase deficiency. N Engl J Med 335: 855–859Google Scholar
  9. 9.
    Msall M, Batshaw ML, Suss R, Brusilow SW, Mellits ED (1984) Neurologic outcome in children with inborn errors of urea synthesis. Outcome of urea-cycle enzymopathies. N Engl J Med 310: 1500–1505Google Scholar
  10. 10.
    Pollitt RJ, Green A, McCabe CJ, Booth A, Cooper NJ, Leonard JV, Nicholl J, Nicholson P, Tunaley JR, Virdi NK (1997) Neonatal screening for inborn errors of metabolism: cost, yield and outcome. Health Technol Assess 1: 1–202Google Scholar
  11. 11.
    Saudubray JM, Touati G, Delonlay P, Jouvet P, Narcy C, Laurent J, Rabier D, Kamoun P, Jan D, Revillon Y (1999) Liver transplantation in urea cycle disorders. Eur J Pediatr 158[Suppl 2]: S55–S59Google Scholar
  12. 12.
    Tluczek A, Mischler EH, Farrell PM, Fost N, Peterson NM, Carey P, Bruns WT, McCarthy C (1992) Parents’ knowledge of neonatal screening and response to false-positive cystic fibrosis testing. J Dev Behav Pediatr 13: 181–186PubMedGoogle Scholar
  13. 13.
    Uchino T, Endo F, Matsuda I (1998) Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J Inherit Metab Dis 21[Suppl 1]: 151–159Google Scholar
  14. 14.
    Wiech N, Clissold D, MacArthur R (1997) Safety and efficacy of buphenyl (sodium phenylbutyrate) tablet and powder (abstract). Advances in Inherited Urea Cycle Disorders, Vienna, Austria, pp 25Google Scholar
  15. 15.
    Wilson JMG, Jungner G (1968) Principles and practice of screening for disease. Public Health Papers WHO 34: 26–39Google Scholar
  16. 16.
    Yudkoff M, Daikhin Y, Ye X, Wilson JM, Batshaw ML (1998) In vivo measurement of ureagenesis with stable isotopes. J Inherit Metab Dis 21: 21–29CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Laboratoire Central de Chimie CliniqueCentre Hospitalier Universitaire Vaudois Lausanne Switzerland

Personalised recommendations