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Neuropediatrics 2026; 57(01): 003-004
DOI: 10.1055/s-0045-1814385
Editorial

Harmless Food Supplement or Medicine with Side Effects—Promising Treatment Options for Neurometabolic Disorders: Explore Well and Proceed with Caution

Authors

  • Saskia B. Wortmann

    1   University Children's Hospital, Paracelsus Medical University (PMU), Salzburg, Austria

  • Ingo Borggraefe

    2   Division of Pediatric Neurology, Department of Pediatrics, Developmental Medicine and Social Pediatrics, Ludwig Maximilian University Munich, University Hospital, Dr. von Hauner Children's Hospital, Munich, Germany
    3   Comprehensive Epilepsy Center for Children and Adolescents, Ludwig Maximilians University Munich, University Hospital, Munich, Germany
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Fueled by the availability of genome-wide sequencing techniques, numerous new gene–disease associations underlying neurometabolic disorders have been identified in the last years. This often not only ends the diagnostic odyssey of the affected individual but also identifies amenable metabolic pathways. Examples are the use of (oral) food supplements like uridine for CAD deficiency, a.k.a. developmental and epileptic encephalopathy 50 (MIM #616457)[1] or the use of the biosynthetic intermediate 4-hydroxybenzoic acid, a food and drug preservative, in the management of coenzyme Q10 biosynthesis disorders like HPDL-deficiency (MIM #619026) or COQ2 (MIM #607426) deficiency.[2] [3]

In the current issue, Himmelreich et al[4] explore the use of the water-soluble vitamin biotin in PMM2-CDG (#212065), a Congenital Disorders of Glycosylation (CDG) sharing the phenotypical features of neurodevelopmental issues, seizures, and movement disorder with biotinidase deficiency (#253260), a neurometabolic disorder well-known to respond to biotin and included in newborn screening programs worldwide.[5]

In another article of this issue, Brands et al.[6] describe a case series of two patients with pyridox(am)ine-5′-phosphate oxidase deficiency (#610090), and two patients with ALDH7A1 deficiency (#266100) who received long-term pyridoxal-5′-phosphate (PLP) treatment. Three of the four patients developed hepatocellular carcinoma after several years of PLP treatment; one developed fully reversible severe hepatotoxicity. These findings raise significant concerns about the long-term hepatic safety of oral PLP in patients with vitamin B6-dependent epilepsies.

Both articles mirror the multiple challenges we all are facing. We often do not know (well enough) the natural history of a disorder and regularly—if not always—face a broad phenotypic spectrum with individual variation in severity and course of disease. This makes it challenging to judge the effectiveness of a treatment. It is further difficult to find an appropriate study design to investigate treatments for rare diseases in general, and in developing children in particular.

Furthermore, the products used to treat these rare diseases are not formally registered as medication. In the European Union (EU), nutritional therapy products are regulated as food supplements, food for special medical purposes, or medication.[7] The requirements and level of oversight increase for each of these categories. Relying on lesser-regulated food products to treat inborn metabolic diseases (IMDs) raises concerns regarding product quality, safety, reimbursement, and patient access.

While the pace of finding new gene–disease associations is slowing down and the big “gene-hunting” time is over, we need to move forward to treatment and collaborate to find meaningful and safe treatments that are available at reasonable costs for all patients.



Publication History

Received: 28 November 2025

Accepted: 01 December 2025

Article published online:
22 January 2026

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