An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients /

Ligia S Almeida; Catarina Pereira; Ruxandra Aanicai; Sabine Schröder; Tomasz Bochinski; Anett Kaune; Alice Urzi; Tania C. L. S Spohr; Nikenza Viceconte; Sebastian Oppermann; Mohammed Alasel; Saeedeh Ebadat; Sana Iftikhar; Eresha Jasinge; Solaf M Elsayed; Hoda Tomoum; Iman Marzouk; Anil B Jalan; Agnė Čerkauskaitė; Rimantė Čerkauskienė; Tinatin Tkemaladze; Anjum Muhammad Nadeem; Iman Gamal El Din Mahmoud; Fawzia Amer Mossad; Mona Kamel; Laila Abdel Selim; Huma Arshad Cheema; Omid Paknia; Claudia Cozma; Carlos Juaristi-Manrique; Pilar Guatibonza-Moreno; Tobias Böttcher; Florian Vogel; Jorge Pinto-Basto; Aida Bertoli-Avella; Peter Bauer; Sabine Schroeder; Tobias Boettcher

doi:10.1038/s41431-022-01119-5

Title	An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients /
Authors	Almeida, Ligia S ; Pereira, Catarina ; Aanicai, Ruxandra ; Schröder, Sabine ; Bochinski, Tomasz ; Kaune, Anett ; Urzi, Alice ; Spohr, Tania C. L. S ; Viceconte, Nikenza ; Oppermann, Sebastian ; Alasel, Mohammed ; Ebadat, Saeedeh ; Iftikhar, Sana ; Jasinge, Eresha ; Elsayed, Solaf M ; Tomoum, Hoda ; Marzouk, Iman ; Jalan, Anil B ; Čerkauskaitė, Agnė ; Čerkauskienė, Rimantė ; Tkemaladze, Tinatin ; Nadeem, Anjum Muhammad ; El Din Mahmoud, Iman Gamal ; Mossad, Fawzia Amer ; Kamel, Mona ; Selim, Laila Abdel ; Cheema, Huma Arshad ; Paknia, Omid ; Cozma, Claudia ; Juaristi-Manrique, Carlos ; Guatibonza-Moreno, Pilar ; Böttcher, Tobias ; Vogel, Florian ; Pinto-Basto, Jorge ; Bertoli-Avella, Aida ; Bauer, Peter ; Schroeder, Sabine ; Boettcher, Tobias
DOI	10.1038/s41431-022-01119-5
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Is Part of	European journal of human genetics.. London : Springer Nature. 2022, vol. 30, p. 1029-1035.. ISSN 1018-4813. eISSN 1476-5438
Abstract [eng]	To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved. Within this cohort, the highest diagnostic yield was obtained for patients from Asia (57.5%, mainly from Pakistan). Overall, 701 pathogenic/likely pathogenic unique SNVs and 40 CNVs were identified. In 620 patients, the result of the biochemical tests guided variant classification and reporting. Top five diagnosed diseases were: Gaucher disease, Niemann-Pick disease type A/B, phenylketonuria, mucopolysaccharidosis type I, and Wilson disease. We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. More importantly, up to 43% of these patients ( n = 610) could benefit from medical treatments (e.g., enzyme replacement therapy). This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs.
Published	London : Springer Nature
Type	Journal article
Language	English
Publication date	2022
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„An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients /“