title: Clinical outcome, biochemical and therapeutic follow-up in 14 Austrian patients with Long-Chain 3-Hydroxy Acyl CoA Dehydrogenase Deficiency (LCHADD).
abstract: BACKGROUND
  LCHADD is a long-fatty acid oxidation disorder with immediate symptoms and long-term complications. We evaluated data on clinical status, biochemical parameters, therapeutic regimens and outcome of Austrian LCHADD patients.
  
  
  METHODS
  Clinical and outcome data including history, diagnosis, short- and long-term manifestations, growth, psychomotor development, hospitalizations, therapy of 14 Austrian patients with LCHADD were evaluated. Biochemically, we evaluated creatine kinase (CK) and acyl carnitine profiles.
  
  
  RESULTS
  All LCHADD patients are homozygous for the common mutation. Three are siblings. Diagnosis was first established biochemically. Nine/14 (64%) were prematures, with IRDS occurring in six. In nine (64%), diagnosis was established through newborn screening, the remaining five (36%) were diagnosed clinically. Four pregnancies were complicated by HELLP syndrome, one by preeclampsia. In two, intrauterine growth retardation and placental insufficiency were reported. Five were diagnosed with hepatopathy at some point, seven with cardiomyopathy and eight with retinopathy, clinically relevant only in one patient. Polyneuropathy is only present in one. Three patients have a PEG, one is regularly fed via NG-tube. Growth is normal in all, as well as psychomotor development, except for two extremely premature girls. In 11 patients, 165 episodes with elevated creatine kinase concentrations were observed with 6-31 (median 14) per patient; three have shown no elevated CK concentrations. Median total carnitine on therapy was 19 μmol/l (range 11-61). For 14 patients, there have been 181 hospitalizations (median 9 per patient), comprising 1337 in-patient-days. All centres adhere to treatment with a fat-defined diet; patients have between 15% and 40% of their energy intake from fat (median 29%), out of which between 20% and 80% are medium-chain triglycerides (MCT) (median 62%). Four patients have been treated with heptanoate (C7).
  
  
  CONCLUSIONS
  Our data show LCHADD outcome can be favourable. Growth and psychomotor development is normal, except in two prematures. Frequency of CK measurements decreases with age, correlating with a decreasing number of hospitalizations. About 50% develop complications affecting different organ systems. There is no relevant difference between the patients treated in the respective centers. Concluding from single case reports, anaplerotic therapy with heptanoate should be further evaluated.
authors.affiliation: Medical University of Innsbruck, Clinic for Pediatrics, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria. daniela.karall@i-med.ac.at.
authors.forename: Daniela
authors.initials: D
authors.lastname: Karall
authors.affiliation: University Children's Hospital, Graz, Austria. Michaela.Brunner-Krainz@klinikum-graz.at.
authors.forename: Michaela
authors.initials: M
authors.lastname: Brunner-Krainz
authors.affiliation: Medical University of Innsbruck, Clinic for Pediatrics, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria. catareenah@gmail.com.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kogelnig
authors.affiliation: University Children's Hospital, Vienna, Austria. vassiliki.konstantopoulou@meduniwien.ac.at.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Konstantopoulou
authors.affiliation: Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany. esther.maier@med.uni-muenchen.de.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Maier
authors.affiliation: University Children's Hospital, Vienna, Austria. dorothea.moeslinger@meduniwien.ac.at.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Möslinger
authors.affiliation: University Children's Hospital, Zürich, Switzerland. Barbara.plecko@kispi.uzh.ch.
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.affiliation: University Children's Hospital, Salzburg, Austria. w.sperl@salk.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
authors.affiliation: University Children's Hospital, Salzburg, Austria. b.volkmar@salk.at.
authors.forename: Barbara
authors.initials: B
authors.lastname: Volkmar
authors.affiliation: Medical University of Innsbruck, Clinic for Pediatrics, Inherited Metabolic Disorders, Anichstrasse 35, 6020, Innsbruck, Austria. sabine.scholl-buergi@uki.at.
authors.forename: Sabine
authors.initials: S
authors.lastname: Scholl-Bürgi
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D000293:Adolescent; D009202:Cardiomyopathies / Q000178:diet therapy* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004750:Enteral Nutrition; D005227:Fatty Acids / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D007441:Intubation, Gastrointestinal; D008052:Lipid Metabolism, Inborn Errors / Q000178:diet therapy* / Q000473:pathology; D008297:Male; D017240:Mitochondrial Myopathies / Q000178:diet therapy* / Q000473:pathology; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency; D009422:Nervous System Diseases / Q000178:diet therapy* / Q000473:pathology; D012189:Retrospective Studies; D012206:Rhabdomyolysis / Q000178:diet therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D005227:Fatty Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063991:Mitochondrial Trifunctional Protein