Precision medicine in neurometabolic diseases: Timing shapes neurodevelopment

Irreversible brain injury frequently precedes the development of recognizable clinical phenotypes in neurometabolic diseases.1 In the absence of timely and appropriate treatment, these disorders are associated with high early mortality and substantial morbidity. Affected children may present within the first weeks or months of life with epileptic encephalopathy or rapidly progressive motor regression, leading to profound developmental delay and long-term neurological sequelae. Precision medicine therefore represents a critical clinical approach in the management of neurometabolic diseases, with the potential to enable earlier diagnosis, targeted interventions, and meaningful improvement in neurological outcomes. For decades, the diagnosis of neurometabolic diagnosis has relied on clinical phenotype recognition and serial biochemical assays. Precision medicine fundamentally reframes this approach by prioritizing diagnostic speed and elucidation of underlying molecular pathogenic mechanisms. In this context, newborn screening (NBS)—once limited to a small number of neurometabolic disorders—has evolved into a form of population-based precision medicine. Laboratory evaluations such as tandem mass spectrometry, multiplex enzyme assays, and second-tier genetic testing have enabled the early detection of a lot of neurometabolic diseases, like lysosomal storage diseases, peroxisomal disorders, and monoamine neurotransmitter disorders.2-4 Experience from large-scale NBS programs, such as those in Taiwan, highlight the feasibility of expansion while underscoring its inherent complexity, particularly in light of the limited predictive value of screening biomarkers for neurological severity. The neurological implications of expanded NBS underscore a major challenge in balancing early intervention against unpredictability of disease severity. Difficulty in predicting neurological outcomes at birth may complicate treatment decisions and raises ethical concerns, especially when effective therapies are limited or unavailable. While precision medicine cannot fully resolve these challenges, it provides a framework for risk stratification through the integration of biochemical, genetic, and other laboratory data. In addition to NBS, rapid genomic sequencing has become an essential part for the diagnosis of critically ill neonates.2, 3 Rapid whole-exome or whole-genome sequencing can now establish a genetic diagnosis within days, substantially shortening the diagnostic delay for neonates presenting with intractable seizures or encephalopathy. Importantly, rapid genomic testing not only increases diagnostic yield but may also directly influence therapeutic decisions and subsequent neurological outcomes. In neurometabolic diseases, early genetic diagnosis can support the initiation of vitamin or cofactor supplementation, guide targeted metabolic therapies, such as ketogenic diet, or, in some cases, inform redirection toward palliative care in children. Therapeutic outcomes in precision medicine are nevertheless variable.4 Vitamin-responsive epilepsies, such as pyridoxine-dependent epilepsy, and disorders such as glucose transporter type 1 deficiency illustrate how early genetic diagnosis can prevent permanent neurological injury. Gene therapies further represent a paradigm shift from supportive management toward disease-modifying intervention, with neurological outcomes highly depending on the time of diagnosis and treatment. In lysosomal storage diseases, precision medicine increasingly emphasizes the importance of neurological risk classification and the development of targeted central nervous system-directed approach alongside systemic enzyme replacement.4 However, significant barriers to implementation remain, including the cost and availability of genetic diagnostics and advanced therapies. Addressing these challenges will require more international registries and collaboration, harmonized outcome measures, and collaborative approaches to reach the consensus in treatment. Neurometabolic diseases are also frequently associated with a broad spectrum of movement disorders, including dystonia, ataxia, chorea, myoclonus, and parkinsonism, reflecting the preferential involvement of basal ganglia and cerebellar networks.5 Movement disorders may represent the early or predominant manifestation of diseases. Precision medicine, through early targeted metabolic or gene-based therapy, also has the potential to prevent disease progression or mitigate the severity of movement disorders, particularly when treatment is initiated before irreversible motor circuit injury occurs. The International Child Neurology Congress ('Connecting the Dots, Mapping the Future') will be held from 25th to 29th May 2026, in Taipei, Taiwan. The congress will highlight recent advances in precision medicine for neurometabolic diseases and movement disorders, with emphasis on updated diagnostic approach and evolving treatment strategies in different pediatric neurological disorders. The congress aims to bridge translational research and clinical care, shape future directions in child neurology, and provide a valuable opportunity for neurologists worldwide. Not required.