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Insulin-dependent diabetes mellitus secretory diarrhea syndrome(IPEX)

MedGen UID:
83339
Concept ID:
C0342288
Disease or Syndrome
Synonyms: Autoimmunity-immunodeficiency syndrome X-linked; DIABETES MELLITUS, CONGENITAL INSULIN-DEPENDENT, WITH FATAL SECRETORY DIARRHEA; Diarrhea, polyendocrinopathy, fatal infection syndrome, X-linked; Enteropathy, autoimmune, with hemolytic anemia and polyendocrinopathy; IDDM secretory diarrhea syndrome; Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome; IMMUNODEFICIENCY, POLYENDOCRINOPATHY, AND ENTEROPATHY, X-LINKED; Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked; IPEX; IPEX and IPEX-Like; Polyendocrinopathy, immune dysfunction and diarrhea X-linked; X-linked autoimmunity-allergic dysregulation syndrome
SNOMED CT: X-linked immune dysregulation, polyendocrinopathy, enteropathy syndrome (724276006); Autoimmune enteropathy type 1 (724276006)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): FOXP3 (Xp11.23)
 
Monarch Initiative: MONDO:0010580
OMIM®: 304790
Orphanet: ORPHA37042

Disease characteristics

Excerpted from the GeneReview: IPEX Syndrome
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is characterized by systemic autoimmunity, typically beginning in the first year of life, which includes the triad of enteropathy (manifesting as malabsorption and watery diarrhea), endocrinopathy (most commonly type 1 insulin-dependent diabetes mellitus), and eczematous dermatitis. In addition to these manifestations, many children have other autoimmune phenomena including cytopenias, autoimmune hepatitis, nephropathy, lymphadenopathy, splenomegaly, alopecia, arthritis, and interstitial lung disease related to immune dysregulation. Fetal presentation of IPEX syndrome includes hydrops, echogenic bowel, skin desquamation, intrauterine growth deficiency, and fetal akinesia. Without aggressive immunosuppression or hematopoietic stem cell transplantation (HSCT), the majority of affected males will die within the first one to two years of life from metabolic derangements, severe malabsorption, or sepsis. Individuals with a milder phenotype have survived into the second or third decade of life, but this is uncommon. [from GeneReviews]
Authors:
Queenie K-G Tan  |  Raymond J Louie  |  John W Sleasman   view full author information

Additional descriptions

From OMIM
IPEX is an X-linked recessive immunologic disorder characterized by onset in infancy of severe diarrhea due to enteropathy, type 1 diabetes mellitus, and dermatitis. Other features may include hypothyroidism, autoimmune hemolytic anemia, thrombocytopenia, lymphadenopathy, hepatitis, and nephritis. The disorder may be fatal before age 2 years if not aggressively treated. Long-term therapeutic options include immunosuppression and hematopoietic stem cell transplantation (review by d'Hennezel et al., 2012).  http://www.omim.org/entry/304790
From MedlinePlus Genetics
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome primarily affects males and is caused by problems with the immune system. The immune system normally protects the body from foreign invaders, such as bacteria and viruses, by recognizing and attacking these invaders and clearing them from the body. However, the immune system can malfunction and attack the body's own tissues and organs instead, which is known as autoimmunity. IPEX syndrome is characterized by the development of multiple autoimmune disorders in affected individuals. Although IPEX syndrome can affect many different areas of the body, autoimmune disorders involving the intestines, skin, and hormone-producing (endocrine) glands occur most often. IPEX syndrome can be life-threatening in early childhood.

Almost all individuals with IPEX syndrome develop a disorder of the intestines called autoimmune enteropathy. Autoimmune enteropathy occurs when certain cells in the intestines are destroyed by a person's immune system. It causes severe diarrhea, which is usually the first symptom of IPEX syndrome. Autoimmune enteropathy typically begins in the first few months of life. It can cause failure to gain weight and grow at the expected rate (failure to thrive) and general wasting and weight loss (cachexia).

People with IPEX syndrome frequently develop inflammation of the skin, called dermatitis. Eczema is the most common type of dermatitis that occurs in this syndrome, and it causes abnormal patches of red, irritated skin. Other skin disorders that cause similar symptoms are sometimes present in IPEX syndrome.

The term polyendocrinopathy is used in IPEX syndrome because individuals can develop multiple disorders of the endocrine glands. Type 1 diabetes mellitus is an autoimmune condition involving the pancreas and is the most common endocrine disorder present in people with IPEX syndrome. It usually develops within the first few months of life and prevents the body from properly controlling the amount of sugar in the blood. Autoimmune thyroid disease may also develop in people with IPEX syndrome. The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. This gland is commonly underactive (hypothyroidism) in individuals with this disorder, but may become overactive (hyperthyroidism).

Individuals with IPEX syndrome typically develop other types of autoimmune disorders in addition to those that involve the intestines, skin, and endocrine glands. Autoimmune blood disorders are common; about half of affected individuals have low levels of red blood cells (anemia), platelets (thrombocytopenia), or certain white blood cells (neutropenia) because these cells are attacked by the immune system. In some individuals, IPEX syndrome involves the liver and kidneys.  https://medlineplus.gov/genetics/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatitis
MedGen UID:
5515
Concept ID:
C0019158
Disease or Syndrome
Inflammation of the liver.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Villous atrophy
MedGen UID:
154306
Concept ID:
C0554101
Finding
The enteric villi are atrophic or absent.
Ileus
MedGen UID:
219874
Concept ID:
C1258215
Disease or Syndrome
Acute obstruction of the intestines preventing passage of the contents of the intestines.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Coombs-positive hemolytic anemia
MedGen UID:
105458
Concept ID:
C0520736
Disease or Syndrome
A type of hemolytic anemia in which the Coombs test is positive.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Erythroderma
MedGen UID:
3767
Concept ID:
C0011606
Disease or Syndrome
An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.
Eosinophilia
MedGen UID:
41824
Concept ID:
C0014457
Disease or Syndrome
Increased count of eosinophils in the blood.
Glomerulonephritis
MedGen UID:
6616
Concept ID:
C0017658
Disease or Syndrome
Inflammation of the renal glomeruli.
Increased circulating IgE level
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargment (swelling) of a lymph node.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Immune dysregulation
MedGen UID:
335001
Concept ID:
C1844666
Finding
Altered immune function characterized by lymphoid proliferation, immune activation, and excessive autoreactivity often leading to autoimmune/inflammatory complications.
Anti-glutamic acid decarboxylase antibody positivity
MedGen UID:
1370651
Concept ID:
C4476703
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against glutamic acid decarboxylase.
Food allergy
MedGen UID:
1635115
Concept ID:
C4554344
Disease or Syndrome
Primary food allergies primarily occur as a result (most likely) of gastrointestinal sensitization to predominantly stable food allergens (glycoproteins). A secondary food allergy develops after primary sensitization to airborne allergens (e. g., pollen allergens) with subsequent reactions (due to cross-reactivity) to structurally related often labile allergens in (plant) foods.
Severe infection
MedGen UID:
1700844
Concept ID:
C5139167
Disease or Syndrome
A type of infection that is regarded as a sign of a pathological susceptibility to infection because of unusual severity or intensity of the infection.
Diabetes mellitus type 1
MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVInsulin-dependent diabetes mellitus secretory diarrhea syndrome
Follow this link to review classifications for Insulin-dependent diabetes mellitus secretory diarrhea syndrome in Orphanet.

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