X-Linked immune dysregulation, polyendocrinopathy, and enteropathy (IPEX) syndrome with concurrent membranous and IgA...

X-linked immune dysregulation, polyendocrinopathy, and enteropathy (IPEX) syndrome is a rare X-linked disorder caused by mutations in the forkhead box P3 (FOXP3) gene. It typically presents very early in life with the classic triad of intractable diarrhea, type 1 diabetes mellitus, and dermatitis. Kidney involvement has been reported in a substantial minority of patients with IPEX syndrome, with membranous nephropathy being the most frequent biopsy pattern.

In this case report, we describe a 15-year-old boy who developed type 1 diabetes mellitus at age one year and later developed difficult-to-control asthma, eczema-like skin rashes, and food allergies. At nine years of age, he was noted to have increasing creatinine levels and proteinuria. Kidney biopsy revealed overlapping features of membranous and immunoglobulin A (IgA) nephropathy. Genetic testing identified a hemizygous pathogenic variant in FOXP3 (c·1040 G > A, p.Arg347His), establishing a diagnosis of IPEX syndrome. Despite supportive management, his kidney function continued to decline, progressing to stage V chronic kidney disease, and he is now awaiting hematopoietic stem cell transplantation. This case highlights an unusual kidney presentation of IPEX syndrome.

The coexistence of membranous and IgA nephropathy may have contributed to the rapid progression of the disease. Clinicians should consider IPEX syndrome in children with kidney disease accompanied by autoimmune endocrinopathies or allergic features, even if the classic gastrointestinal involvement is missing.