Clinical Case of Immune Dysregulation, Polyendocrinopaty, Enteropathy, X-Linked (IPEX) Syndrome with Severe Immune Deficiency and Late Onset of Endocrinopathy and Enteropathy

Abstract

Objective. To describe the clinical characteristics of IPEX syndrome in a child with FOXP3 mutation. Clinical Case. A boy aged 2.3 years was born from first normal pregnancy with a weight of 3420 gr. Family History. Two brothers of the mother died before the age of 3 years with severe infections, diarrhea, erythroderma, and elevated immunoglobulins class E (IgEs). Since first month of life, our patient suffered from septicemia, pneumonias, pyelonephritis, and meningitis, accompanied with eczematous dermatitis and IgEs up to 4000 IU/L (normal <10). At the age of 1.6 years, he developed type 1 diabetes mellitus (T1DM). He was underweighted (−3.42 SDS) and had some phenotypic features like coarse face, muscle hypotonia, joint hyperextensibility, eczematous dermatitis, and subcutaneous cold abscesses. Autoimmune thyroiditis and celiac disease were excluded. After diabetes, intermittent watery diarrhea appeared with progression to severe intractable form. Finally, aggravating symptoms of nephritis, cachexia, and respiratory insufficiency were the cause for his death at the age of 2 years and 3 months. The DNA analysis at the University of Exeter Medical School established mutation at exon 10 of FOXP3 gene c.1010G >A, p. (Arg337Gln), which confirmed IPEX syndrome. The same mutation in heterozygotic state was found in the mother. A prenatal diagnosis of her second pregnancy ensured a daughter carrier of the mutation.

Clinical, Genetic, and Biochemical Characteristics of Early-Onset Diabetes in the Finnish Population

“…Case 21, now a 20-year old male with neonatal-onset diabetes and a hemizygous missense mutation R337Q in the FOXP3 gene, had a very similar phenotype as the patients described earlier with the IPEX syndrome caused by FOXP3 mutations (30,36). His two older brothers with the same syndrome without diabetes died at the age of 6 months and 19 years.…”

“…Gene variants in K-ATP channel genes accounted for 36% of the monogenic cases which is less than reported in other Caucasian populations (30). Single mutations in GCK (G261 and novel del 212) (22), RFX6 and in FOXP3 (30,36) as well as the previously published STAT3 mutation (23) associated with diabetes in sporadic families. In addition, targeted sequencing revealed several gene variants (Suppl.…”

Primary immunodeficiencies associated with eosinophilia

“…T cells are quantitatively normal with normal proliferative responses to mitogens and antigens; however, Treg cells are markedly reduced or absent [ 94 – 96 ]. High IgE and eosinophilia are frequently reported in IPEX patients [ 92 , 97 , 98 ].…”

IPEX syndrome: an easily-missed diagnosis of a life threatening condition

“…1), in addition to thyroiditis (30%), recurrent infections (20%) and less common additional autoimmune conditions like autoimmune cytopenias, nephritis, pneumonitis, hepatitis, arthritis, myositis and vasculitis. 5,7,8 Manifestations of IPEX syndrome usually appear sequentially, and the affected organ spectrum varies from one patient to another. 5 Without treatment, IPEX syndrome is usually fatal within the first 2 years of life due to life-threatening infections, severe watery diarrhea and diabetic ketoacidosis.…”