Neurological outcome in long-chain hydroxy fatty acid oxidation disorders
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Neurological outcome in long-chain hydroxy fatty acid oxidation disorders. / Mütze, Ulrike; Ottenberger, Alina; Gleich, Florian; Maier, Esther M; Lindner, Martin; Husain, Ralf A; Palm, Katja; Beblo, Skadi; Freisinger, Peter; Santer, René; Thimm, Eva; Vom Dahl, Stephan; Weinhold, Natalie; Grohmann-Held, Karina; Haase, Claudia; Hennermann, Julia B; Hörbe-Blindt, Alexandra; Kamrath, Clemens; Marquardt, Iris; Marquardt, Thorsten; Behne, Robert; Haas, Dorothea; Spiekerkoetter, Ute; Hoffmann, Georg F; Garbade, Sven F; Grünert, Sarah C; Kölker, Stefan.
in: ANN CLIN TRANSL NEUR, Jahrgang 11, Nr. 4, 04.2024, S. 883-898.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Neurological outcome in long-chain hydroxy fatty acid oxidation disorders
AU - Mütze, Ulrike
AU - Ottenberger, Alina
AU - Gleich, Florian
AU - Maier, Esther M
AU - Lindner, Martin
AU - Husain, Ralf A
AU - Palm, Katja
AU - Beblo, Skadi
AU - Freisinger, Peter
AU - Santer, René
AU - Thimm, Eva
AU - Vom Dahl, Stephan
AU - Weinhold, Natalie
AU - Grohmann-Held, Karina
AU - Haase, Claudia
AU - Hennermann, Julia B
AU - Hörbe-Blindt, Alexandra
AU - Kamrath, Clemens
AU - Marquardt, Iris
AU - Marquardt, Thorsten
AU - Behne, Robert
AU - Haas, Dorothea
AU - Spiekerkoetter, Ute
AU - Hoffmann, Georg F
AU - Garbade, Sven F
AU - Grünert, Sarah C
AU - Kölker, Stefan
N1 - © 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2024/4
Y1 - 2024/4
N2 - OBJECTIVE: This study aims to elucidate the long-term benefit of newborn screening (NBS) for individuals with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide.METHODS: German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long-term clinical outcomes.RESULTS: Sixty-seven individuals with LCHAD/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4 years; p = 0.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved.INTERPRETATION: While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long-term morbidity in screened individuals with LCHAD/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course-altering treatment.
AB - OBJECTIVE: This study aims to elucidate the long-term benefit of newborn screening (NBS) for individuals with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide.METHODS: German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long-term clinical outcomes.RESULTS: Sixty-seven individuals with LCHAD/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4 years; p = 0.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved.INTERPRETATION: While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long-term morbidity in screened individuals with LCHAD/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course-altering treatment.
KW - Infant, Newborn
KW - Humans
KW - Child
KW - Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase/metabolism
KW - Lipid Metabolism, Inborn Errors/diagnosis
KW - Mitochondrial Trifunctional Protein/metabolism
KW - Fatty Acids/metabolism
KW - Cardiomyopathies
KW - Nervous System Diseases
KW - Rhabdomyolysis
KW - Mitochondrial Myopathies
U2 - 10.1002/acn3.52002
DO - 10.1002/acn3.52002
M3 - SCORING: Journal article
C2 - 38263760
VL - 11
SP - 883
EP - 898
JO - ANN CLIN TRANSL NEUR
JF - ANN CLIN TRANSL NEUR
SN - 2328-9503
IS - 4
ER -
