Treatment Outcomes for Maple Syrup Urine Disease Detected by Newborn Screening

Author:

Mengler Katharina1,Garbade Sven F.1,Gleich Florian1,Thimm Eva2,May Petra3,Lindner Martin4,Lüsebrink Natalia4,Marquardt Thorsten5,Hübner Vanessa6,Krämer Johannes7,Neugebauer Julia8,Beblo Skadi9,Gillitzer Claus10,Grünert Sarah C.11,Hennermann Julia B.12,Kamrath Clemens13,Marquardt Iris14,Näke Andrea10,Murko Simona15,Schmidt Sebastian16,Schnabel Elena1,Lommer-Steinhoff Svenja1,Hoffmann Georg F.1,Beime Jan15,Santer René15,Kölker Stefan1,Mütze Ulrike1

Affiliation:

1. aMedical Faculty of Heidelberg, Center for Child and Adolescent Medicine, Division of Child Neurology and Metabolic Medicine, Heidelberg University, Heidelberg, Germany

2. bDepartment of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children’s Hospital

3. cClinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany

4. dDivision of Pediatric Neurology, University Children’s Hospital Frankfurt, Frankfurt, Germany

5. eDepartment of Pediatrics, University Hospital Muenster, Muenster, Germany

6. fChildren’s Hospital Reutlingen, Klinikum am Steinenberg, Reutlingen, Germany

7. gDepartment of Pediatric and Adolescent Medicine, University of Ulm, Ulm, Germany

8. hCorporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Center of Chronically Sick Children, Charité - Universitätsmedizin Berlin, Berlin, Germany

9. iDepartment of Women and Child Health, Hospital for Children and Adolescents, Center for Pediatric Research Leipzig (CPL), University Hospitals, University of Leipzig, Leipzig, Germany

10. jChildren’s Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany

11. kDepartment of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany

12. lVilla Metabolica, Center for Pediatric and Adolescent Medicine, Mainz University Medical Center, Mainz, Germany

13. mCenter of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany

14. nDepartment of Child Neurology, Children’s Hospital Oldenburg, Oldenburg, Germany

15. oDepartment of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany

16. pClinic for Internal Medicine III, Endocrinology and Metabolic Diseases, University Hospital Jena

Abstract

OBJECTIVE Maple syrup urine disease (MSUD), a life-threatening metabolic disorder, is included in newborn screening (NBS) programs worldwide. The study aims to evaluate the impact of NBS on the long-term outcome of MSUD patients. METHODS We performed a prospective, national, multicenter, observational study. RESULTS In the studied NBS cohort (N = 33; 22 classic MSUD [cMSUD], 11 variant MSUD [vMSUD]; median age at last visit 10.4 years), 32 (97%) patients survived, 58% of them had normal cognitive functions (median IQ 87). Initial peak leucine increased linearly with age in cMSUD (median: 1712 µmol/L), but not in vMSUD. Global IQ correlated inversely with the initial peak leucine concentration (P = .04; β = –0.0081) and the frequency of decompensations (P = .02; β = –9.133). A cluster analysis identified 2 subgroups differing in their long-term metabolic control (median leucine concentration: 162 vs 278 µmol/L; P < .001). In cMSUD, lower leucine concentrations were associated with a higher IQ (95.5 vs 80; P = .008). Liver transplantation (median age 5.8 years) was not associated with better cognitive outcome. NBS is highly sensitive for cMSUD, but vMSUD might be missed (N = 2 missed by NBS). CONCLUSIONS NBS and the early start of treatment improve survival and long-term outcome in individuals with cMSUD. Disease severity is an important modifier of outcome; however, the time to NBS report and the quality of long-term metabolic control had an independent impact on cognitive outcome, highlighting the importance of an early diagnosis and the quality of treatment.

Publisher

American Academy of Pediatrics (AAP)

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