Early-onset refractory diarrhea due to immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome associated with a novel mutation in the FOXP3 gene: A case report

Abstract

BACKGROUND

Immune dysregulation, polyendocrinopthy, enteropathy, X-linked (IPEX) syndrome is a rare X-linked recessive disease caused by mutations in the forkhead box protein 3 (FOXP3) gene, which is a master transcriptional regulator for the development and function of CD4⁺CD25⁺ regulatory T (Treg) cells. The dysfunction of these cells leads to multiple system autoimmune diseases. We present a case of IPEX due to a mutation not reported in the literature before.

CASE SUMMARY

We report a male patient with IPEX syndrome who presented with refractory diarrhea and malabsorption leading to failure to thrive, as well as with hypothyroidism and nephrotic syndrome. Laboratory investigation showed increased total IgE and Treg cells, decreased free triiodothyronine (FT3) and free thyroxine (FT4), and proteinuria. Multiple dietary and supportive treatments were introduced but did not improve the diarrhea during his hospital stay. Ultimately, whole exome sequencing revealed that the patient was hemizygous for the exon 5, c.542G>A (p.Ser181Asn) mutation of the FOXP3 gene, which has not been previously reported. The patient remains on prednisone and euthyrox while awaiting hematopoietic stem cell transplantation at the time of the compilation of this case report.

CONCLUSION

We report a novel FOXP3 gene mutation involved in IPEX. A high level of suspicion should be maintained in an early-onset refractory diarrhea patient.

Keywords: Immune dysregulation, polyendocrinopthy, enteropathy, X-linked syndrome; Forkhead box protein 3; Mutation; Refractory diarrhea; Regulatory T cells; Case report

Core tip: Immune dysregulation, polyendocrinopthy, enteropathy, X-linked syndrome is a rare X-linked recessive disease caused by mutations in the FOXP3 gene. Patients most commonly present symptoms with refractory diarrhea, type 1 diabetes mellitus, eczema, and rarely, symptoms of nephrotic syndrome, hypothyroidism, and thrombocytopenia. Herein, we present a patient with refractory diarrhea, failure to thrive, hypothyroidism, and nephrotic syndrome who was subsequently found to have a novel mutation in the FOXP3 gene [c.542G>A (p.Ser181Asn)]. Patients with immune dysregulation, polyendocrinopthy, enteropathy, X-linked generally require supportive treatments and replacement therapy, such as steroids, immunosuppressors, or hematopoietic stem cell transplantation.