Inherited metabolic disorders in adults: systematic review on patient characteristics and diagnostic yield of broad sequencing techniques (exome and genome sequencing).
| العنوان: | Inherited metabolic disorders in adults: systematic review on patient characteristics and diagnostic yield of broad sequencing techniques (exome and genome sequencing). |
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| المؤلفون: | Ferreira EA; Department of Paediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; United for Metabolic Diseases, Amsterdam, Netherlands., Buijs MJN; United for Metabolic Diseases, Amsterdam, Netherlands.; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Wijngaard R; United for Metabolic Diseases, Amsterdam, Netherlands.; Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands., Daams JG; Medical Library (J.G.D.), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Datema MR; Department of Endocrinology and Metabolism, Amsterdam UMC, Research Institute Gastroenterology, Endocrinology and Metabolism (AGEM), University of Amsterdam, Amsterdam, Netherlands., Engelen M; Department of Pediatric Neurology/Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands., van Karnebeek CDM; Department of Paediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; United for Metabolic Diseases, Amsterdam, Netherlands.; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Oud MM; United for Metabolic Diseases, Amsterdam, Netherlands.; Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands., Vaz FM; Department of Paediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; Laboratory of Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, Gastroenterology, Endocrinology & Metabolism (AGEM), University of Amsterdam, Amsterdam University Medical Center, Amsterdam, Netherlands., Wamelink MMC; Laboratory of Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, Gastroenterology, Endocrinology & Metabolism (AGEM), University of Amsterdam, Amsterdam University Medical Center, Amsterdam, Netherlands., van der Crabben SN; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands., Langeveld M; Department of Endocrinology and Metabolism, Amsterdam UMC, Research Institute Gastroenterology, Endocrinology and Metabolism (AGEM), University of Amsterdam, Amsterdam, Netherlands. |
| المصدر: | Frontiers in neurology [Front Neurol] 2023 Jul 25; Vol. 14, pp. 1206106. Date of Electronic Publication: 2023 Jul 25 (Print Publication: 2023). |
| نوع المنشور: | Systematic Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101546899 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2295 (Print) Linking ISSN: 16642295 NLM ISO Abbreviation: Front Neurol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation, 2010]- |
| مستخلص: | Background/objectives: The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD in adults is difficult, because phenotypes are different from those in children and influenced by symptoms from acquired conditions. This systematic literature review aims to answer the following questions: (1) What is the diagnostic yield of exome/genome sequencing (ES/GS) for IMD in adults with unsolved phenotypes? (2) What characteristics do adult patients diagnosed with IMD through ES/GS have? Methods: A systematic search was conducted using the following search terms (simplified): "Whole exome sequencing (WES)," "Whole genome sequencing (WGS)," "IMD," "diagnostics" and the 1,450 known metabolic genes derived from ICIMD. Data from 695 articles, including 27,702 patients, were analyzed using two different methods. First, the diagnostic yield for IMD in patients presenting with a similar phenotype was calculated. Secondly, the characteristics of patients diagnosed with IMD through ES/GS in adulthood were established. Results: The diagnostic yield of ES and/or GS for adult patients presenting with unexplained neurological symptoms is 11% and for those presenting with dyslipidemia, diabetes, auditory and cardiovascular symptoms 10, 9, 8 and 7%, respectively. IMD patients diagnosed in adulthood (n = 1,426), most frequently portray neurological symptoms (65%), specifically extrapyramidal/cerebellar symptoms (57%), intellectual disability/dementia/psychiatric symptoms (41%), pyramidal tract symptoms/myelopathy (37%), peripheral neuropathy (18%), and epileptic seizures (16%). The second most frequently observed symptoms were ophthalmological (21%). In 47% of the IMD diagnosed patients, symptoms from multiple organ systems were reported. On average, adult patients are diagnosed 15 years after first presenting symptoms. Disease-related abnormalities in metabolites in plasma, urine or cerebral spinal fluid were identified in 40% of all patients whom underwent metabolic screening. In 52% the diagnosis led to identification of affected family members with the same IMD. Conclusion: ES and/or GS is likely to yield an IMD diagnosis in adult patients presenting with an unexplained neurological phenotype, as well as in patients with a phenotype involving multiple organ systems. If a gene panel does not yield a conclusive diagnosis, it is worthwhile to analyze all known disease genes. Further prospective research is needed to establish the best diagnostic approach (type and sequence of metabolic and genetic test) in adult patients presenting with a wide range of symptoms, suspected of having an IMD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021295156. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Ferreira, Buijs, Wijngaard, Daams, Datema, Engelen, Karnebeek, Oud, Vaz, Wamelink, Crabben and Langeveld.) |
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| فهرسة مساهمة: | Keywords: adults; diagnostics; exome sequencing; genome sequencing; genomics; inherited metabolic disorders (IMD); metabolic |
| تواريخ الأحداث: | Date Created: 20230810 Latest Revision: 20230811 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10408679 |
| DOI: | 10.3389/fneur.2023.1206106 |
| PMID: | 37560457 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1664-2295 |
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| DOI: | 10.3389/fneur.2023.1206106 |