Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system
| Autor: | Shimul Chowdhury, David Dimmock, Nanda Ramchandar, Charlotte A. Hobbs, Yan Ding, Stephen F. Kingsmore, Kiely N. James, Shareef Nahas, Anna-Kaisa Niemi, Annette Feigenbaum, Wendy Benson |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Research Report
Male Resuscitation medicine.medical_specialty upper limb spasticity Genotype poor suck Day of life Clinical Decision-Making Cyclic pyranopterin monophosphate Disease generalized tonic seizures infantile encephalopathy Polymorphism Single Nucleotide chemistry.chemical_compound congenital horizontal nystagmus Infant Mortality medicine Humans Precision Medicine Intensive care medicine Molybdenum cofactor deficiency Alleles Metal Metabolism Inborn Errors Newborn screening Whole Genome Sequencing Neonatal encephalopathy business.industry Infant Newborn diffuse swelling of cerebral white matter Disease Management Infant General Medicine medicine.disease Precision medicine Phenotype chemistry hypouricemia Disease Susceptibility business Delivery of Health Care |
| Zdroj: | Cold Spring Harbor Molecular Case Studies |
| ISSN: | 2373-2873 |
| Popis: | Neonatal encephalopathy with seizures is a presentation in which rapid whole-genome sequencing (rWGS) has shown clinical utility and improved outcomes. We report a neonate who presented on the third day of life with seizures refractory to antiepileptic medications and neurologic and computerized tomographic findings consistent with severe generalized brain swelling. rWGS revealed compound heterozygous variants in the molybdenum cofactor synthesis gene, type 1A (MOCS1 c.*7 + 5G > A and c.377G > A); a provisional diagnosis of molybdenum cofactor deficiency on day of life 4. An emergency investigational new drug application for intravenous replacement of the MOCS1 product, cyclic pyranopterin monophosphate, was considered, but felt unsuitable in light of the severity of disease and delay in the start of treatment. The patient died on day of life 9 despite having a precise molecular diagnosis within the first week of life. This case illustrates that an rWGS-based molecular diagnosis within the first week of life may be insufficient to improve outcomes. However, it did inform clinical decision-making with regard to resuscitation and predicted long-term outcome. We suggest that to achieve optimal reductions in morbidity and mortality, rWGS must be implemented within a comprehensive rapid precision medicine system (CRPM). Akin to newborn screening (NBS), CRPM will have onboarding, diagnosis, and precision medicine implementation components developed in response to patient and parental needs. Education of health-care providers in a learning model in which ongoing data analyses informs system improvement will be essential for optimal effectiveness of CRPM. |
| Databáze: | OpenAIRE |
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