TY  - JOUR
A1  - Repp, Birgit M.
A1  - Mastantuono, Elisa
A1  - Alston, Charlotte
A1  - Schiff, Manuel
A1  - Haack, Tobias
A1  - Rötig, Agnes
A1  - Ardissone, Anna
A1  - Lombès, Anne
A1  - Catarino, Claudia B.
A1  - Diodato, Daria
A1  - Schottmann, Gudrun
A1  - Poulton, Joanna
A1  - Burlina, Alberto
A1  - Jonckheere, An
A1  - Munnich, Arnold
A1  - Rolinski, Boris
A1  - Ghezzi, Daniele
A1  - Rokicki, Dariusz
A1  - Wellesley, Diana
A1  - Martinelli, Diego
A1  - Wenhong, Ding
A1  - Lamantea, Eleonora
A1  - Ostergaard, Elsebet
A1  - Pronicka, Ewa
A1  - Pierre, Germaine
A1  - Smeets, Hubert J. M.
A1  - Wittig, Ilka
A1  - Scurr, Ingrid
A1  - De Coo, Irenaeus F. M.
A1  - Moroni, Isabella
A1  - Smet, Joél
A1  - Mayr, Johannes A.
A1  - Dai, Lifang
A1  - Meirleir, Linda de
A1  - Schülke-Gerstenfeld, Markus
A1  - Zeviani, Massimo
A1  - Morscher, Raphael J.
A1  - McFarland, Robert
A1  - Seneca, Sara
A1  - Klopstock, Thomas
A1  - Meitinger, Thomas
A1  - Wieland, Thomas
A1  - Strom, Tim-Matthias
A1  - Herberg, Ulrike
A1  - Ahting, Uwe
A1  - Sperl, Wolfgang
A1  - Nassogne, Marie-Cécile
A1  - Ling, Han
A1  - Fang, Fang
A1  - Freisinger, Peter
A1  - Coster, Rudy van
A1  - Strecker, Valentina
A1  - Taylor, Robert W.
A1  - Häberle, Johannes
A1  - Vockley, Jerry
A1  - Prokisch, Holger
A1  - Wortmann, Saskia
T1  - Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency : is riboflavin supplementation effective?
T2  - Orphanet journal of rare diseases
N2  - Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy.
Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation.
Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers.
Conclusions: Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin.
KW  - Complex I
KW  - Cardiomyopathy
KW  - Heart transplantation
KW  - Mitochondrial disorder
KW  - Lactic acidosis
KW  - Treatment
KW  - Prognosis
KW  - Neonatal
KW  - Vitamin
KW  - Activities of daily living
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47166
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-471666
SN  - 1750-1172
N1  - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 13
IS  - 1, Art. 120
SP  - 1
EP  - 10
PB  - BioMed Central
CY  - London
ER  -