title: Urgent metabolic service improves survival in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency detected by symptomatic identification and pilot newborn screening.
abstract: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a fatty acid oxidation disorder with especially high mortality and uncertain long-term outcome. The aim of the study was to analyze the influence of diagnostic approach on survival in 59 affected children. Referral to a metabolic center was replaced over time by urine/blood testing in centralized metabolic laboratory (selective screening) and by pilot tandem mass spectrometry newborn screening (NBS). Molecular analysis revealed the prevalent mutation in the HADHA gene in all 58 examined cases. Twenty patients died. The number of detections and number of deaths were respectively 9 and 4 (44%) in the patients recognized by differential diagnosis, 28 and 9 (32%) - by selective screening, and 11 and 1 (9%) - by NBS. In 80% of cases the death occurred before or within 3 weeks from the identification. Urgent and active metabolic service remarkably influenced the surviving. The current age of 39 survivors is 0.5 to 23 yrs (mean 7.2 yrs). The disease frequency estimated on the patients number was 1: 115 450, whereas in the pilot NBS - 1: 109 750 (658 492 neonates tested). Interestingly, the phenylalanine level in asymptomatic neonates frequently exceeded the cut-off values.
  
  
  CONCLUSIONS
  1) Urgent metabolic intervention decreases mortality of LCHAD-deficient patients, but the prognosis is still uncertain. 2) Emergent metabolic reporting and service are crucial also for the survival of neonates detected by NBS. 3) The nationwide selective screening appeared efficient in LCHADD detection in the country. 4) Transient mild hyperphenylalaninaemia may occur in LCHAD-deficient newborns.
authors.affiliation: Department of Metabolic Diseases, Endocrinology and Diabetology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sykut-Cegielska
authors.forename: Wanda
authors.initials: W
authors.lastname: Gradowska
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.forename: Brage S
authors.initials: BS
authors.lastname: Andresen
authors.forename: Rikke K J
authors.initials: RK
authors.lastname: Olsen
authors.forename: Mariusz
authors.initials: M
authors.lastname: Ołtarzewski
authors.forename: Maciej
authors.initials: M
authors.lastname: Pronicki
authors.forename: Magdalena
authors.initials: M
authors.lastname: Pajdowska
authors.forename: Anna
authors.initials: A
authors.lastname: Bogdańska
authors.forename: Ewa
authors.initials: E
authors.lastname: Jabłońska
authors.forename: Barbara
authors.initials: B
authors.lastname: Radomyska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kuśmierska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Niels
authors.initials: N
authors.lastname: Gregersen
authors.forename: Ewa
authors.initials: E
authors.lastname: Pronicka
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000652:urine; D000293:Adolescent; D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D003890:Desiccation; D004636:Emergency Service, Hospital / Q000458:organization & administration; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal / Q000458:organization & administration; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000652:urine; D015997:Neonatal Screening / Q000379:methods* / Q000458:organization & administration; D010808:Physical Examination / Q000379:methods*; D010865:Pilot Projects; D012150:Polymorphism, Restriction Fragment Length; D013534:Survival; D013997:Time Factors; D016482:Urinalysis / Q000379:methods
chemical_list: C116917:acylcarnitine; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D002331:Carnitine