Two cases of Inborn errors of immunity in a Mennonite population in Chihuahua.

Introduction: Inborn errors of immunity (IEI), have demonstrated a higher prevalence among Mennonites residing in northern Mexico. We present two IEI cases in Cuauhtémoc, Chihuahua: A Severe Combined Immunodeficiency (SCID) resulting from a CD3δ mutation, and a case involving a G6PC3 mutation leading to severe congenital neutropenia.
Case 1: An 8-year-old male, was admitted at 2 months of age for severe pneumonia. A month later, He developed suppurative otitis, oral ulcers, and fever. Further investigations revealed severe neutropenia (170 neutrophils) with normal immunoglobulin levels, interatrial communication, cryptorchidism, and abdominal collateral veins. Exome sequencing revealed an autosomal recessive variant: G6PC3c.482G>A;p (Arg161Gln). He is currently thriving, undergoing G-CSF treatment.
Case 2: A 5-month-old male, was hospitalized for respiratory distress, myocarditis and multisystem inflammatory syndrome linked to SARS-CoV-2, requiring broad-spectrum antibiotics and intravenous immunoglobulin. He had a remarkable family history of a sibling who died during early infancy and a cousin with CD3δ-SCID. Immunology panels reported IgG: 468mg/dL, IgA: <19mg/dL, IgM: 27mg/dL, CD3: 40 total cells, CD4: 20 cells, CD8: 44 cells, CD16-56: 1096 cells, CD19: 1676 cells, 2658 absolute lymphocytes. T− B+NK+ SCID was suspected. Exome sequencing revealed homozygous CD3δ and heterozygous ADA mutations. Following a Hematopoietic Stem Cell Transplant from his father, a 100% chimerism was achieved, with no acute graft-versus-host disease. After 2 years after the transplant, he remains healthy.
Discussion: IEI frequently emerges in genetically limited populations, such as the Mennonite groups that immigrated to Mexico during the past century. Cases of ataxia-telangiectasia and SCID resulting from ADA/ZAP70 deficiencies have been documented previously. CD3δ mutations hinder T-cell development with early SCID onset. Similarly, G6PC3 deficiency manifests as severe congenital neutropenia, cardiopathies, and hepatic/urogenital anomalies. To our knowledge, this represents the first G6PC3-deficiency case described in Mennonites, highlighting the need for IEI awareness and early diagnosis in this population.

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