Defects in NEUROG3 cause an autosomal recessive disorder characterized by intestinal malabsorption and enteroendocrine cell defects associated with early onset diabetes. Few cases are reported.

A 16-year-old male with a history of severe diarrhea from one week of age. He was hospitalized several times due to diarrhea, hydroelectrolytic alterations and metabolic acidosis. Exocrine pancreatic insufficiency and hyperglycemia were detected at school age, and was referred to the third level of care.
At 15, presented generalized dermatosis with erythemato-squamous plaques, pustular psoriasis confirmed by biopsy, persisted with diarrhea up to 10 L/day, severe malnutrition, and was sent to the immunology service. Autoimmune enteropathy was suspected, intestinal biopsies showed CD4+ CD20+ lymphocytic infiltrate in lamina propia, CD3+/CD8+ (epithelial), with suspicion of an autoimmune component.

He has normal lymphocyte and immunoglobulin counts, positive antinuclear antibodies, positive HLA-B27. Brain MRI reports vasculitis lesions and an old infarct area. MRI of the hips showed bilateral sacroiliitis. Due to the high suspicion of autoimmunity, treatment with IVIG, methylprednisolone, cyclosporine, and mycophenolate was started, presenting a very evident clinical response with complete resolution of diarrhea and skin lesions, adequate weight gain and resolution of sacroiliitis, achieving better glycemic control. Cyclosporine was suspended, and anti-TNFa (adalimumab) was added to the management. Genetic sequencing panel for IEI was performed, reporting a homozygous pathogenic variant in NEUROG3 (c.319 C>A (p.Arg107Ser).

Defects in NEUROG3 are described as mainly associated with diabetes, chronic diarrhea, and malabsorption from an early age. The genetic defect results in the absence of enteroendocrine cells, which explains the poor response to conventional treatments for diarrhea. The association of NEUROG3 defects with autoimmune pathologies has not been reported. The clinical presentation, histopathology, presence of autoantibodies, and rapid response to treatment in our patient suggest an inflammatory/autoimmune component in this pathology that should be considered and studied further.

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