Beyond Newborn Screening: Clinical Outcomes and Genotypic Spectrum Underlying Maple Syrup Urine Disease in Mexico.
4 affiliations
- 1Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.
- 2Laboratorio de Biología Molecular, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.
- 3Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, National Autonomous University of Mexico (UNAM), Mexico City 04530, Mexico.
- 4Servicio de Endocrinología, Hospital de la Niñez Oaxaqueña, Oaxaca 71294, Mexico.
Abstract
Maple syrup urine disease (MSUD) is a time-critical inborn error of metabolism in which early detection may prevent irreversible neurological injury, yet the success of newborn screening (NBS) depends on timely post-screening care. We retrospectively characterized the clinical, biochemical, and genotypic spectrum of 88 Mexican patients from 80 unrelated families evaluated between 1995 and 2026 and assessed the relationship between NBS, treatment timing, neurological outcome, and survival. Most patients had severe neonatal disease, and 73/88 (83%) presented with acute metabolic decompensation requiring hospitalization. Nine patients were identified by NBS: six received timely confirmatory diagnosis and treatment and maintained normal age-appropriate neurodevelopment during 10 years of follow-up, whereas three experienced delays in the diagnostic and therapeutic pathway, developed metabolic decompensation, and subsequently had severe neurological disability. None of the successfully screened patients died. Among 33 molecularly characterized unrelated patients, 31 distinct variants were identified in BCKDHA, BCKDHB, and DBT, with marked genotypic heterogeneity. These findings show that National NBS strategies should prioritize the inclusion of this time critical disorder and the shortening of the interval between a positive screening result and treatment initiation. MSUD NBS should serve as the entry point to an optimal continuum of care. Rapid confirmation, immediate referral, treatment initiation, and sustained specialized metabolic follow-up are essential for translating early detection into favorable outcomes.
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BibTeX
@article{velaamieva2026beyond,
title = {{Beyond Newborn Screening: Clinical Outcomes and Genotypic Spectrum Underlying Maple Syrup Urine Disease in Mexico.}},
author = {Marcela Vela-Amieva and Miriam Erandi Reyna-Fabián and Liliana Fernández-Hernández and Sara Guillén-López and Lizbeth López-Mejía and Miguel Angel Alcantara-Ortigoza and Ariadna Gonzalez-Del Angel and Bernardette Estandía-Ortega and Isabel Ibarra-González and Laura Paz-Castillo and Cynthia Fernández-Lainez},
journal = {International journal of neonatal screening},
year = {2026},
month = oct,
doi = {10.3390/ijns12040083},
url = {https://europepmc.org/article/MED/42924760},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beyond Newborn Screening: Clinical Outcomes and Genotypic Spectrum Underlying Maple Syrup Urine Disease in Mexico.
AU - Marcela Vela-Amieva
AU - Miriam Erandi Reyna-Fabián
AU - Liliana Fernández-Hernández
AU - Sara Guillén-López
AU - Lizbeth López-Mejía
AU - Miguel Angel Alcantara-Ortigoza
AU - Ariadna Gonzalez-Del Angel
AU - Bernardette Estandía-Ortega
AU - Isabel Ibarra-González
AU - Laura Paz-Castillo
AU - Cynthia Fernández-Lainez
PY - 2026
DA - 2026/10/09
JO - International journal of neonatal screening
DO - 10.3390/ijns12040083
UR - https://europepmc.org/article/MED/42924760
AB - Maple syrup urine disease (MSUD) is a time-critical inborn error of metabolism in which early detection may prevent irreversible neurological injury, yet the success of newborn screening (NBS) depends on timely post-screening care. We retrospectively characterized the clinical, biochemical, and genotypic spectrum of 88 Mexican patients from 80 unrelated families evaluated between 1995 and 2026 and assessed the relationship between NBS, treatment timing, neurological outcome, and survival. Most patients had severe neonatal disease, and 73/88 (83%) presented with acute metabolic decompensation requiring hospitalization. Nine patients were identified by NBS: six received timely confirmatory diagnosis and treatment and maintained normal age-appropriate neurodevelopment during 10 years of follow-up, whereas three experienced delays in the diagnostic and therapeutic pathway, developed metabolic decompensation, and subsequently had severe neurological disability. None of the successfully screened patients died. Among 33 molecularly characterized unrelated patients, 31 distinct variants were identified in BCKDHA, BCKDHB, and DBT, with marked genotypic heterogeneity. These findings show that National NBS strategies should prioritize the inclusion of this time critical disorder and the shortening of the interval between a positive screening result and treatment initiation. MSUD NBS should serve as the entry point to an optimal continuum of care. Rapid confirmation, immediate referral, treatment initiation, and sustained specialized metabolic follow-up are essential for translating early detection into favorable outcomes.
SN - 2409-515X
ER -