title: Cross-sectional observational study of 208 patients with non-classical urea cycle disorders.
abstract: Urea cycle disorders (UCDs) are inherited disorders of ammonia detoxification often regarded as mainly of relevance to pediatricians. Based on an increasing number of case studies it has become obvious that a significant number of UCD patients are affected by their disease in a non-classical way: presenting outside the newborn period, following a mild course, presenting with unusual clinical features, or asymptomatic patients with only biochemical signs of a UCD. These patients are surviving into adolescence and adulthood, rendering this group of diseases clinically relevant to adult physicians as well as pediatricians. In preparation for an international workshop we collected data on all patients with non-classical UCDs treated by the participants in 20 European metabolic centres. Information was collected on a cohort of 208 patients 50% of which were ≥ 16 years old. The largest subgroup (121 patients) had X-linked ornithine transcarbamylase deficiency (OTCD) of whom 83 were female and 29% of these were asymptomatic. In index patients, there was a mean delay from first symptoms to diagnosis of 1.6 years. Cognitive impairment was present in 36% of all patients including female OTCD patients (in 31%) and those 41 patients identified presymptomatically following positive newborn screening (in 12%). In conclusion, UCD patients with non-classical clinical presentations require the interest and care of adult physicians and have a high risk of neurological complications. To improve the outcome of UCDs, a greater awareness by health professionals of the importance of hyperammonemia and UCDs, and ultimately avoidance of the still long delay to correctly diagnose the patients, is crucial.
authors.affiliation: Division of Metabolism, University Children's Hospital, Steinwiesstr. 75, 8032, Zurich, Switzerland.
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Rüegger
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.forename: Diana
authors.initials: D
authors.lastname: Ballhausen
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Baumgartner
authors.forename: Skadi
authors.initials: S
authors.lastname: Beblo
authors.forename: Anibh
authors.initials: A
authors.lastname: Das
authors.forename: Matthias
authors.initials: M
authors.lastname: Gautschi
authors.forename: Esther M
authors.initials: EM
authors.lastname: Glahn
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Grünert
authors.forename: Julia
authors.initials: J
authors.lastname: Hennermann
authors.forename: Michel
authors.initials: M
authors.lastname: Hochuli
authors.forename: Martina
authors.initials: M
authors.lastname: Huemer
authors.forename: Daniela
authors.initials: D
authors.lastname: Karall
authors.forename: Stefan
authors.initials: S
authors.lastname: Kölker
authors.forename: Robin H
authors.initials: RH
authors.lastname: Lachmann
authors.forename: Amelie
authors.initials: A
authors.lastname: Lotz-Havla
authors.forename: Dorothea
authors.initials: D
authors.lastname: Möslinger
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nuoffer
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.forename: Frank
authors.initials: F
authors.lastname: Rutsch
authors.forename: René
authors.initials: R
authors.lastname: Santer
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
authors.forename: Christian
authors.initials: C
authors.lastname: Staufner
authors.forename: Tamar
authors.initials: T
authors.lastname: Stricker
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.forename: Monique
authors.initials: M
authors.lastname: Williams
authors.forename: Peter
authors.initials: P
authors.lastname: Burgard
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001120:Arginine / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002956:Citrulline / Q000627:therapeutic use; D003072:Cognition Disorders / Q000150:complications; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004035:Diet Therapy; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D015997:Neonatal Screening; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D055815:Young Adult
chemical_list: D002956:Citrulline; D001120:Arginine