Outcomes after newborn screening for propionic and methylmalonic acidemia and homocystinurias

Abstract: The current German newborn screening (NBS) panel includes 13 inherited metabolic diseases (IMDs). In addition, a NBS pilot study in Southwest Germany identifies individuals with propionic acidemia (PA), methylmalonic acidemia (MMA), combined and isolated remethylation disorders (e.g., cobalamin [cbl] C and methylenetetrahydrofolate reductase [MTHFR] deficiency), cystathionine β-synthase (CBS) deficiency, and neonatal cbl deficiency through one multiple-tier algorithm. The long-term health benefits of screened individuals are evaluated in a multicenter observational study. Twenty seven screened individuals with IMDs (PA [N = 13], MMA [N = 6], cblC deficiency [N = 5], MTHFR deficiency [N = 2] and CBS deficiency [N = 1]), and 42 with neonatal cbl deficiency were followed for a median of 3.6 years. Seventeen screened IMD patients (63%) experienced at least one metabolic decompensation, 14 of them neonatally and six even before the NBS report (PA, cbl-nonresponsive MMA). Three PA patients died despite NBS and immediate treatment. Fifteen individuals (79%) with PA or MMA and all with cblC deficiency developed permanent, mostly neurological symptoms, while individuals with MTHFR, CBS, and neonatal cbl deficiency had a favorable clinical outcome. Utilizing a combined multiple-tier algorithm, we demonstrate that NBS and specialized metabolic care result in substantial benefits for individuals with MTHFR deficiency, CBS deficiency, neonatal cbl deficiency, and to some extent, cbl-responsive MMA and cblC deficiency. However, its advantage is less evident for individuals with PA and cbl-nonresponsive MMA.

Synopsis
Early detection through newborn screening and subsequent specialized metabolic care improve clinical outcomes and survival in individuals with MTHFR deficiency and cystathionine-β-synthase deficiency, and to some extent in cobalamin-responsive methylmalonic acidemia (MMA) and cblC deficiency while the benefit for individuals with propionic acidemia and cobalamin-nonresponsive MMA is less evident due to the high (neonatal) decompensation rate, mortality, and long-term complications

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Journal of inherited metabolic disease. - 47, 4 (2024) , 674-689, ISSN: 1573-2665

Klassifikation und Themen

• Klassifikation: Medizin, Gesundheit

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2024
• Urheber: Reischl-Hajiabadi, Anna Theresa ; Schnabel, Elena Ana ; Gleich, Florian ; Mengler, Katharina ; Lindner, Martin ; Burgard, Peter ; Posset, Roland ; Lommer‐Steinhoff, Svenja ; Grünert, Sarah ; Thimm, Eva ; Freisinger, Peter ; Hennermann, Julia B. ; Krämer, Johannes ; Gramer, Gwendolyn ; Lenz, Dominic ; Christ, Stine ; Hörster, Friederike ; Hoffmann, Georg F. ; Garbade, Sven ; Kölker, Stefan ; Mütze, Ulrike

Weitere Informationen

• DOI: 10.1002/jimd.12731
• URN: urn:nbn:de:bsz:25-freidok-2466655
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:53 MEZ