Neurological Outcome in Screened Individuals with LCHAD/MTP Deficiency

Background/Purpose: This study aims to elucidate the long-term benefit of neonatal screening for individuals with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, disorders included in newborn screening (NBS) programs worldwide.

Methods: National multicenter study of individuals with genetically and/or enzymatically 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-six individuals with LCHAD/MTP deficiency were included in the study, thereof 53 identified by NBS. All screened individuals survived the neonatal period, but three with MTP deficiency (11.5%) died during the study period. Despite their positive effect on neonatal mortality, NBS and early treatment did not completely prevent neonatal decompensations (28%), symptomatic disease course (94%), metabolic decompensations (80%), manifestation of cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and neuropathy (22%). 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 therapeutic goals decreased with age, from 75% in the first year of life to 12% at age ten, and consensus group recommendations on dietary management were often not achieved.

Conclusion: 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 for better therapeutic strategies and the development of disease-altering treatment.

Publication History

Article published online:
13 November 2023