A novel mutation and unusual clinical features in a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome

Bae, Keun Wook; Kim, Bo Eun; Choi, Jin‐Ho; Lee, Joo Hoon; Kim, Gu-Hwan; Yoo, Han Wook; Seo, Jong Jin

doi:10.1007/s00431-011-1588-1

Cited by 20 publications

(21 citation statements)

References 26 publications

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“…Neonatal diabetes and nephrotic syndrome were reported as the only clinical features in the surviving 15-year-old patient with mutation V408M of FOXP3 [10]. IPEX was genetically proven in 11-year-old boy with diabetes, pure red cell aplasia, membranous glomerulopathy, and posterior reversible encephalopathy syndrome after a vaccination against influenza virus [22]. These atypical clinical presentations of IPEX indicated existing possible underestimation of the real morbidity.…”

Section: Discussionmentioning

confidence: 99%

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

Savova

Arshinkova

Houghton

et al. 2014

Case Reports in Medicine

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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.

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Section: Discussionmentioning

confidence: 99%

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

Savova

Arshinkova

Houghton

et al. 2014

Case Reports in Medicine

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“…Renal disease can be related either to autoimmunity or to prolonged administration of nephrotoxic drugs. They are generally described as tubulonephropathy (Kobayashi et al, 2001; Otsubo et al, 2011) and nephrotic syndrome (Gambineri et al, 2008; Rubio-Cabezas et al, 2009; An et al, 2011; Otsubo et al, 2011), although interstitial nephritis (Bindl et al, 2005; Patey-Mariaud de Serre et al, 2009; Moes et al, 2010) and membranous glomerulonephritis (Moudgil et al, 2007; Halabi-Tawil et al, 2009; Burroughs et al, 2010; Bae et al, 2011) have also been found in some patients’ histopathological examinations. A rare manifestation associated with the milder forms of IPEX with delayed diagnosis is arthritis involving one or more joints (Wildin et al, 2002; De Benedetti et al, 2006).…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A Paradigm of Immunodeficiency with Autoimmunity

Barzaghi¹,

Passerini²,

Bacchetta³

2012

Front. Immun.

295

277

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Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare monogenic primary immunodeficiency (PID) due to mutations of FOXP3, a key transcription factor for naturally occurring (n) regulatory T (Treg) cells. The dysfunction of Treg cells is the main pathogenic event leading to the multi-organ autoimmunity that characterizes IPEX syndrome, a paradigm of genetically determined PID with autoimmunity. IPEX has a severe early onset and can become rapidly fatal within the first year of life regardless of the type and site of the mutation. The initial presenting symptoms are severe enteritis and/or type-1 diabetes mellitus, alone or in combination with eczema and elevated serum IgE. Other autoimmune symptoms, such as hypothyroidism, cytopenia, hepatitis, nephropathy, arthritis, and alopecia can develop in patients who survive the initial acute phase. The current therapeutic options for IPEX patients are limited. Supportive and replacement therapies combined with pharmacological immunosuppression are required to control symptoms at onset. However, these procedures can allow only a reduction of the clinical manifestations without a permanent control of the disease. The only known effective cure for IPEX syndrome is hematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease. This review aims to summarize the clinical histories and genomic mutations of the IPEX patients described in the literature to date. We will focus on the clinical and immunological features that allow differential diagnosis of IPEX syndrome and distinguish it from other PID with autoimmunity. The efficacy of the current therapies will be reviewed, and possible innovative approaches, based on the latest highlights of the pathogenesis to treat this severe primary autoimmune disease of childhood, will be discussed.

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“…В большинстве случаев IPEX-синдром дебюти-рует сразу после рождения или в течение первого года жизни пациентов [1,2,15]. Клинические про-явления IPEX-синдрома крайне вариабельны.…”

Section: Discussionunclassified

“…ПРОБЛЕМЫ ЭНДОКРИНОЛОГИИ, 5,2014 выявляются у детей старшего возраста [15,19]. Ауто-иммунный тиреоидит -вторая по частоте эндо-кринная патология у пациентов с IPEX-синдромом -чаще всего проявляется гипотиреозом [1].…”

Section: Discussionunclassified

X-linked immune dysregulation, polyendocrinopathy and enteropathy (IPEX syndrome): the description of a clinical case and a short literature review

Тихонович¹,

Петряйкина²,

Рыбкина³

et al. 2014

Probl Endokrinol (Mosk)

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IPEX syndrome (X-linked immune dysregulation, polyendocrinopathy, enteropathy) is one of the rare hereditary X-linked forms of neonatal diabetes mellitus associated with mutations in the FOXP3 gene. The disease is characterized by the combination of polyendocrinopathy (more frequently neonatal diabetes mellitus) with enteropathy and immune dysregulation. In the majority of the cases it has an unfavourable prognosis. The present article presents for the first time in the Russian-speaking literature the description of the genetically verified case of IPEX syndrome.

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A novel mutation and unusual clinical features in a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome

Abstract: Although IPEX syndrome is usually a disease of infancy, it should not be ruled out solely on the basis of age. IPEX presentation is so variable that it should be suspected in a male child with one or more autoimmune disorders and severe infections.

Cited by 20 publications

References 26 publications

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

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

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A Paradigm of Immunodeficiency with Autoimmunity

X-linked immune dysregulation, polyendocrinopathy and enteropathy (IPEX syndrome): the description of a clinical case and a short literature review

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