Inborn errors of immunity in Low German Mennonite communities in Mexico: a case series and narrative literature review.

BACKGROUND: Inborn errors of immunity (IEI) comprise a genetically heterogeneous group of disorders with increased prevalence in consanguineous and endogamous populations due to founder effects. Low German Mennonite (LGM) communities in Mexico represent a high-risk population characterized by genetic isolation and an increased frequency of autosomal recessive conditions. Although IEI have been reported in LGM populations from Canada and Europe, systematic data from Mexican LGM communities remain limited. This study describes four novel clinical cases of IEI in LGM patients evaluated at two tertiary referral centers in Mexico and contextualizes these findings within a comprehensive review of previously reported IEI in this population.

METHODS: A retrospective case series was conducted at two tertiary pediatric referral centers in Mexico between 2020 and 2025, including four patients from LGM communities with clinically and/or genetically confirmed IEI. Clinical, immunological, and genetic data were extracted from medical records. Genetic diagnoses, when available, were established using next-generation sequencing or whole-exome sequencing, with variant classification according to ACMG criteria. A narrative literature search was performed in PubMed, Embase, SciELO, and Web of Science to identify previously reported IEI cases in LGM populations.

RESULTS: Four patients with distinct IEI were identified: one with glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, one with X-linked agammaglobulinemia (XLA) due to a pathogenic variant in the Bruton tyrosine kinase (BTK) gene, and two with severe combined immunodeficiency (SCID). All patients required disease-specific therapy, including granulocyte colony-stimulating factor, immunoglobulin replacement, and/or hematopoietic cell transplantation. The literature review identified a broad spectrum of IEI in LGM populations, including cellular and humoral immunodeficiencies, phagocyte disorders, DNA repair defects, autoinflammatory conditions, and bone marrow failure syndromes.

CONCLUSIONS: This exploratory case series contributes to the growing body of evidence on IEI in LGM populations and highlights the potential impact of founder variants in this community. Given the small sample size and retrospective design, generalization of these findings requires prospective, population-based validation. Early diagnosis through newborn screening, accessible genetic testing, and timely clinical intervention remains essential to improve outcomes.