Neuropediatrics 2023; 54(S 01): S1-S32
DOI: 10.1055/s-0043-1777164
Neuromuskuläre Erkrankungen

Neurological Outcome in Screened Individuals with LCHAD/MTP Deficiency

A. Ottenberger
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
,
U. Mütze
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
,
F. Gleich
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
,
E. M. Maier
2   Ludwig-Maximilians-University, Dr. von Hauner Children's Hospital, München, Deutschland
,
M. Lindner
3   Division of Pediatric Neurology, University Children's Hospital Frankfurt, Frankfurt am Main, Deutschland
,
R. A. Husain
4   Department of Neuropediatrics, Jena University Hospital, Center for Inborn Metabolic Disorders, Jena, Deutschland
,
K. Palm
5   Division of Endocrinology, Diabetology and Metabolic Medicine, University Children's Hospital, Magdeburg, Deutschland
,
S. Beblo
6   Department of Women and Child Health, Hospital for Children and Adolescents, Center for Pediatric Research Leipzig (CPL), University Hospitals, University of Leipzig, Leipzig, Deutschland
,
P. Freisinger
7   Klinikum am Steinenberg, Children's Hospital Reutlingen, Reutlingen, Deutschland
,
R. Santer
8   University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
,
E. Thimm
9   Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Deutschland
,
S. vom Dahl
10   Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University Düsseldorf, University Hospital, Düsseldorf, Deutschland
,
S. Roloff
11   Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Chronically Sick Children, Berlin, Deutschland
,
K. Grohmann-Held
12   Department of Pediatrics and Adolescent Medicine, University Medicine Greifswald, Greifswald, Deutschland
,
C. Haase
13   Department of Pediatrics and Adolescent Medicine, Helios Hospital Erfurt, Erfurt, Deutschland
,
J. B. Hennermann
14   Center for Pediatric and Adolescent Medicine, Mainz University Medical Center, Villa Metabolica, Mainz, Deutschland
,
A. Hörbe-Blindt
15   Clinic Bremen Mitte, Prof.-Hess Children's Hospital, Bremen, Deutschland
,
C. Kamrath
16   Department of General Pediatrics and Neonatology, University Hospital of Gießen and Marburg, Gießen, Deutschland
,
I. Marquardt
17   Department of Child Neurology, Children's Hospital Oldenburg, Oldenburg, Deutschland
,
T. Marquardt
18   Department of General Pediatrics, Metabolic Diseases, University Children's Hospital Muenster, Muenster, Deutschland
,
R. Behne
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
,
D. Haas
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
,
U. Spiekerkoetter
19   Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Deutschland
,
G. F. Hoffmann
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
,
S. F. Garbade
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
,
S. C. Grünert
19   Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Deutschland
,
S. Kölker
1   Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine and Dietmar Hopp Metabolic Center, University Hospital Heidelberg, Heidelberg, Deutschland
› Author Affiliations
 

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

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