Xpid E31.0

XPID is an acronym for "X-linked polyendocrinopathy, immunodeficiency and diarrhea syndrome" and is a very rare congenital multisystemic disease with polyendocrine autoimmune syndromes. XPID is assigned to type 4 of polyendocrine autoimmune syndromes.

< 150 patients have been described so far.

mutation in the FOXP3 gene, which is located on the X chromosome in humans. Therefore, only boys become ill. The FOXP3 gene encodes the forkhead box protein P3 (Scurfin: 4 isoforms are known in humans), a protein that is crucial for the formation of regulatory T cells (TReg). Patients with IPEX syndrome lack Tregs, which means that a variety of autoimmune diseases can develop simultaneously.

Due to X-linked inheritance, boys are mainly affected by XPID, while girls are carriers of a defective FOXP3 gene and only suffer mild disease if the defective FOXP3 gene of the mother and the normal allele of the father are codominant.

Most patients develop insulin-dependent diabetes mellitus (type 1 DM) and severe autoimmune enteropathy with diarrhoea in the first days or weeks of life. The enteropathy leads to malabsorption, electrolyte disorders and failure to thrive. Patients may develop other autoimmune endocrinopathies such as autoimmune thyroiditis with hypo- or hyperthyroidism, autoimmune cytopenia, thrombocytopenia, hemolytic anemia and neutropenia. Clinically, signs of hepatitis, glomerulonephritis, myositis, splenomegaly and/or lymphadenopathy appear. Local or systemic infections (e.g. pneumonia, infections with Staphylococcus aureus, candidiasis) may occur.

Dermatologically, there are eczematous or also psoriasiform, pruriginous symptoms. More rarely alopecia (type Alopecia areata) or onychodystrophy can be observed (Barzaghi F et al. 2012).

Untreated, XPID syndrome is fatal within the first years of life. Currently, a cure is only possible through hematopoietic stem cell transplantation.

1. Barzaghi F et al (2012) Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A Paradigm of Immunodeficiency with Autoimmunity. Front Immunol 3: 211.