Diagnostic delay in inherited metabolic diseases: Insights from the U-IMD registry
Por:
Teinert J, Gleich F, Kozich V, Dionisi-Vici C, Bellusci M, Haas D, Ješina P, Martinelli D, Pérez-Mohand P, Burlina A, Rubert L, Couce ML, Debray FG, Roland D, Gaspar A, Mohnike K, Garbade SF, Scarpa M, Nassogne MC, Tangeraas T, Gasperini S, Garcia-Cazorla A, Mütze U and Kölker S
Publicada:
1 may 2026
Ahead of Print:
24 mar 2026
Resumen:
Purpose: Early diagnosis and timely initiation of treatment have been shown to be crucial to improve clinical outcomes in individuals with inherited metabolic diseases (IMDs). However, comprehensive data on the diagnostic process and the potential diagnostic delay in IMDs are scarce. This study aims to systematically investigate the diagnostic process in IMDs. Methods: Data were obtained from the Unified European registry for Inherited Metabolic Diseases (U-IMD), the patient registry of the European Reference Network MetabERN. Results: Data were available for 3747 individuals with confirmed diagnosis of one of 345 IMDs. Median age at symptom onset was 120 days. The majority of participants were diagnosed after presenting with symptoms, median diagnostic delay in this group was 270 days, with 47.6% experiencing a diagnostic delay of at least 1 year. Diagnostic delay did not seem to have changed substantially within the last 2 decades in this cohort; however, it varied greatly among single IMDs and different IMD disease groups. Conclusion: Diagnostic delay and concomitantly delayed start of specific therapies is a significant risk of poor outcome for individuals with IMDs, highlighting the urgent need to expand newborn screening programs and to establish (ultra-)rapid genome sequencing in critically ill children. (c) 2026 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Filiaciones:
Teinert J:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany
Gleich F:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany
Kozich V:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Department of Pediatrics and Inherited Metabolic Disorders, Charles University - First Faculty of Medicine and General University Hospital, Prague, Czech Republic
Dionisi-Vici C:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Metabolic Diseases and Hepatology, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy
Bellusci M:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Reference Center for Hereditary Metabolic Disorders, Unidad Ciberer U723, Hospital U. 12 de Octubre, Madrid, Spain
Haas D:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany
Ješina P:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Department of Pediatrics and Inherited Metabolic Disorders, Charles University - First Faculty of Medicine and General University Hospital, Prague, Czech Republic
Martinelli D:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Metabolic Diseases and Hepatology, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy
Pérez-Mohand P:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Reference Center for Hereditary Metabolic Disorders, Unidad Ciberer U723, Hospital U. 12 de Octubre, Madrid, Spain
Burlina A:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Inherited Metabolic Diseases and Newborn Screening, University Hospital, Padova, Italy
Rubert L:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Malattie Metaboliche Ereditarie, Centro Regionale per lo Screening la Diagnosi e la Terapia delle malattie Metaboliche Ereditarie, Verona, Italy
Couce ML:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Hospital Clínico Universitario de Santiago de Compostela, IDIS, RICORS-SAMID, Facultad de Medicina USC, Santiago de Compostela, Spain
Debray FG:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Metabolic Unit, Department of Medical Genetics, CHU Liège, Liège, Belgium
Roland D:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Centre des maladies héréditaires du métabolisme, Département de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium
Gaspar A:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Unidade Local de Saúde de Santa Maria, Lisboa, Portugal
Mohnike K:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Otto-von-Guericke-University Medical Faculty, Magdeburg, Germany
Garbade SF:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany
Scarpa M:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Regional Coordinating Center for Rare Diseases, Udine University Hospital, Udine, Italy
Nassogne MC:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Neurologie Pédiatrique et Maladies héréditaires du Métabolisme, Cliniques universitaires Saint-Luc, UCLouvain, Bruxelles, Belgium
Tangeraas T:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Department of Newborn Screening, Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
Gasperini S:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
Garcia-Cazorla A:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Inborn Errors of Metabolism Unit, Neurology Department, Institut de Recerca Sant Joan de Déu, and CIBERER-ISCIII, Barcelona, Spain
Mütze U:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany
Kölker S:
MetabERN, European Reference Network for Hereditary Metabolic Disorders
Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany
Green Submitted, Green Published, hybrid
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