Neurological outcome in long-chain hydroxy fatty acid oxidation disorders.
Ann Clin Transl Neurol
; 11(4): 883-898, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38263760
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rabdomiólisis
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Miopatías Mitocondriales
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Proteína Trifuncional Mitocondrial
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Errores Innatos del Metabolismo Lipídico
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Cardiomiopatías
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Enfermedades del Sistema Nervioso
Tipo de estudio:
Clinical_trials
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Guideline
Límite:
Child
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Child, preschool
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Humans
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Infant
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Newborn
Idioma:
En
Año:
2024
Tipo del documento:
Article