Maple syrup urine disease: clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the republic of Ireland
Abstract
Since 1972, 18 patients (10 females/8 males) have been detected by newborn bloodspot screening (NBS) with neonatal-onset maple syrup urine disease (MSUD) in Ireland. Patients were stratified into three clusters according to clinical outcome at the time of data collection, including developmental, clinical, and IQ data. A fourth cluster comprised of two early childhood deaths; a third patient died as an adult. We present neuroimaging and electroencephalography together with clinical and biochemical data. Incidence of MSUD (1972-2018) was 1 in 147 975. Overall good clinical outcomes were achieved with 15/18 patients alive and with essentially normal functioning (with only the lowest performing cluster lying beyond a single SD on their full scale intelligence quotient). Molecular genetic analysis revealed genotypes hitherto not reported, including a possible digenic inheritance state for the BCKDHA and DBT genes in one family. Treatment has been based on early implementation of emergency treatment, diet, close monitoring, and even dialysis in the setting of acute metabolic decompensation. A plasma leucine ≥400 μmol/L (outside therapeutic range) was more frequently observed in infancy or during adolescence, possibly due to infections, hormonal changes, or noncompliance. Children require careful management during metabolic decompensations in early childhood, and this represented a key risk period in our cohort. A high level of metabolic control can be achieved through diet with early implementation of a "sick day" regime and, in some cases, dialysis as a rescue therapy. The Irish cohort, despite largely classical phenotypes, achieved good outcomes in the NBS era, underlining the importance of early diagnosis and skilled multidisciplinary team management.
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Excessive branched-chain amino acid concentrations are considered toxic and can cause tissue damage, particularly in the central nervous system.
“Excessive BCAA concentrations are considered toxic and can cause tissue damage, particularly in the CNS (338).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [338]
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Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
- Authors
- O'Reilly, D., Crushell, E., Hughes, J., Ryan, S., Rogers, Y., Borovickova, I., Mayne, P., Riordan, M., Awan, A., Carson, K., Hunter, K., Lynch, B., Shahwan, A., Rüfenacht, V., Häberle, J., Treacy, E. P., Monavari, A. A., & Knerr, I.
- Affiliations
- National Centre for Inherited Metabolic Disorders Children's Health Ireland at Temple Street Dublin Ireland
- Temple Street Children's University Hospital (IE)
- Metabolic Laboratory Children's Health Ireland at Temple Street Dublin Ireland
- University Children's Hospital Zurich (CH)
- Mater Misericordiae University Hospital (IE)
- Corresponding author
- Knerr, Ina
- ORCID
- Venue
- Journal of Inherited Metabolic Disease
- Publisher
- Wiley
- Published
- 2020-12-20
- Volume
- 44
- Issue
- 3
- Pages
- 639-655
- ISSN
- 0141-8955 (ISSN-L)
- 1573-2665
- OpenAlex
- W3112798639
- Cited by
- 24
- References
- 46
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 4
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Inherited Metabolic Disease (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- maple syrup urine disease, newborn bloodspot screening, BCKDHA, DBT, genotype-phenotype correlation, digenic inheritance, metabolic decompensation, plasma leucine, dialysis, metabolic control, intellectual disability, developmental outcomes, incidence, Republic of Ireland
- MeSH terms
- Adolescent, Child, Child, Preschool, Female, Genotype, Humans, Infant, Infant, Newborn, Ireland, Leucine, Male, Maple Syrup Urine Disease, Phenotype, Retrospective Studies, Neonatal Screening, Diet, Protein-Restricted, Early Diagnosis, Dried Blood Spot Testing
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