Vaccination of children with inborn errors of metabolism: safety, immunogenicity, and practical implications

Children with inborn errors of metabolism (IEMs) are vulnerable to infection-induced catabolism and metabolic decompensation, yet vaccination may be delayed because of concerns that fever or reduced intake after immunization could produce similar effects. This review evaluates vaccine safety, immunogenicity, effectiveness, and practical precautions in pediatric IEMs. PubMed/MEDLINE and Embase were searched from inception to 30 June 2026 using predefined terms for IEMs, vaccination, and pediatric populations. Google Scholar and the reference lists of relevant publications were searched as supplementary sources. Primary evidence synthesis was restricted to pediatric studies or separately extractable pediatric results. Mixed-age studies without separable pediatric outcomes were retained only as contextual evidence and were explicitly identified. Study selection and data extraction were performed independently by two reviewers, and findings were synthesized narratively. Pediatric evidence, predominantly from small observational studies, did not identify a consistent signal of increased serious adverse events or metabolic decompensation after vaccination of clinically stable children with IEMs. Limited pediatric studies reported measurable humoral responses, but the evidence is insufficient for many individual disorders and does not establish clinical effectiveness. Published guidance generally favors age-appropriate vaccination, with precautions individualized to metabolic stability, catabolic risk, immune dysfunction, comorbidities, treatment, and vaccine excipients.

Available pediatric evidence is limited but generally reassuring for vaccination of clinically stable children with IEMs. Current guidance supports vaccination according to national schedules unless a vaccine-specific contraindication is present. Decisions concerning live vaccines, serological testing, additional doses, and peri-vaccination measures should be individualized according to the complete immune and metabolic phenotype.

• Infections can precipitate metabolic decompensation in children with IEMs, but vaccination is often delayed because of safety concerns. • Evidence on vaccine immunogenicity and disease-specific precautions remains limited.

• Direct pediatric evidence is limited and heterogeneous but has not identified a consistent safety signal after vaccination of clinically stable children with IEMs. • This review separates pediatric findings from mixed-age contextual evidence and translates published guidance into phenotype-based practical considerations, while highlighting the low certainty of the evidence.