Pediatric immunology · ITCH Deficiency

How ITCH Deficiency Affects the Body

At a Glance

ITCH deficiency can cause variable immune-system inflammation in children, affecting the intestines, liver, lungs, hormone-producing glands, skin, joints, and eyes. Families should recognize warning signs of breathing distress, liver failure, sepsis, dehydration, and diabetic ketoacidosis.

Because the ITCH protein is meant to regulate immune cells throughout the entire body, its absence can lead to inflammation in almost any organ system. However, ITCH deficiency is highly variable. One child may struggle primarily with digestive issues, while another may have mostly lung and skin problems ^[1]^[2]. It is important to remember that these are reported possibilities based on a small number of cases, not a guaranteed checklist for your child. Understanding the range of involvement can help you and your medical team stay vigilant.

The Digestive System and Liver

Digestive and liver issues are among the most common and serious reported features of ITCH deficiency.

Very-Early-Onset Inflammatory Bowel Disease (VEO-IBD): Many children develop severe gut inflammation, often before the age of six. This can appear as enteropathy (general intestinal disease) or colitis (inflammation of the colon), leading to persistent diarrhea, abdominal pain, and blood in the stool ^[2]^[3].
Autoimmune Hepatitis: The immune system may attack the liver, causing chronic inflammation. If left untreated, this can progress to cirrhosis (scarring of the liver) ^[4]^[5].
Pancreatic and Nutrition Issues: Some children may have exocrine pancreatic insufficiency, where the pancreas doesn’t produce enough enzymes to digest food properly, contributing to failure to thrive or poor weight gain ^[6]^[2].

The Respiratory System

Lung involvement often starts with what looks like common infections but can become chronic over time.

Recurrent Infections: Children may have frequent or unusually severe bouts of pneumonia ^[6].
Chronic Lung Disease: Over time, repeated inflammation can lead to bronchiectasis, a condition where the airways become permanently widened and scarred ^[6]^[3]. In severe cases, this has led to a need for long-term oxygen or mechanical ventilation ^[3].

Endocrine and Growth Manifestations

The immune system can also target the glands that produce essential hormones.

Diabetes and Thyroid: Conditions like Type 1 diabetes (where the body cannot regulate blood sugar) and hypothyroidism (an underactive thyroid) have been reported in some individuals ^[2]^[5].
Growth and Development: Most children with ITCH deficiency experience short stature or failure to thrive. Some children also face global developmental delay or intellectual disability, though others have normal cognitive development ^[6]^[1].

Skin, Joints, and Eyes

Inflammation can also occur in the body’s “outer” systems:

Skin: Persistent, red, scaly patches known as psoriasis are common ^[2].
Joints: Some children develop inflammatory arthritis, causing pain and swelling in the joints ^[3].
Eyes: Uveitis (inflammation inside the eye) can occur and requires monitoring by an ophthalmologist to protect vision ^[2].

Red Flags: When to Seek Urgent Care

While most symptoms of ITCH deficiency develop over time, some situations require immediate medical attention. You should have a written emergency plan in place with your child’s specialist. Important note: Immunosuppressive medications can mask a fever, so serious infections can occur without a high fever.

Potential Emergency	Signs to Watch For	Action Required
Acute Liver Failure	Yellowing of the eyes or skin (jaundice), extreme sleepiness, unusual bruising or bleeding, or a swollen abdomen ^[4].	Call 911 or go to the nearest ER immediately.
Severe Respiratory Distress	Rapid breathing, “sucking in” at the ribs or neck, blue-tinted lips, or an inability to catch their breath ^[3]^[6].	Call 911 or go to the nearest ER immediately.
Sepsis (Severe Infection)	Shivering, rapid heart rate, confusion, low temperature, or acting much sicker than usual (even without high fever) ^[4].	Call 911 or go to the nearest ER immediately.
Severe Dehydration	Due to worsening diarrhea (enteropathy), signs include fewer wet diapers, no tears when crying, or a sunken soft spot on an infant’s head ^[5].	Contact your team’s urgent-care line or go to the ER.
Diabetic Ketoacidosis	(If Type 1 Diabetes is suspected): Repeated vomiting, extreme thirst, frequent urination, deep/rapid breathing. ^[2]	Call 911 or go to the nearest ER immediately.

Every child’s journey with ITCH deficiency is unique. By tracking your child’s specific symptoms and working closely with a multidisciplinary team, you can help manage these challenges and respond quickly when needed.

Common questions in this guide

Which parts of the body can ITCH deficiency affect?

ITCH deficiency can cause immune-system inflammation in many parts of the body. Reported areas include the intestines and liver, lungs, hormone-producing glands, skin, joints, and eyes. The pattern is different for each child, so these possible effects are not a checklist that every child will have.

What digestive or liver problems are linked to ITCH deficiency?

Children may develop very-early-onset inflammatory bowel disease, causing ongoing diarrhea, belly pain, or blood in the stool. Autoimmune hepatitis can inflame the liver and may progress to cirrhosis if untreated. Some children also have pancreatic enzyme problems that contribute to poor weight gain.

What lung complications should families watch for?

Repeated or unusually severe pneumonia can lead to chronic lung disease called bronchiectasis, in which the airways become widened and scarred. Severe lung involvement may cause breathing distress and, in some cases, require long-term oxygen or mechanical ventilation. A child’s team may recommend lung function testing or imaging based on the child’s situation.

When is ITCH deficiency an emergency?

Call emergency services or go to the emergency room for severe breathing trouble, blue lips, or signs of acute liver failure such as yellow skin or eyes with unusual sleepiness or bleeding. Suspected diabetic ketoacidosis, including repeated vomiting, extreme thirst, frequent urination, or deep rapid breathing, also requires immediate emergency care. Contact the care team’s urgent line or go to the emergency room for severe dehydration from diarrhea.

Can my child have a serious infection without a fever?

Yes. Immunosuppressive medicines can hide a fever, so a serious infection may instead appear as shivering, a rapid heartbeat, confusion, a low temperature, or a child who seems much sicker than usual. Call the child’s medical team promptly or seek emergency care if these signs occur.

How can ITCH deficiency affect growth and development?

Many children have short stature or poor weight gain, and some have global developmental delay or intellectual disability. Other children have normal cognitive development. The care team can track growth and development over time and arrange a developmental evaluation when needed.

What screening should my child have for ITCH deficiency complications?

Ask the specialist how often your child needs checks for liver inflammation, thyroid disease, and type 1 diabetes. Monitoring may also include liver blood tests such as bilirubin and INR, lung testing or imaging, eye examinations, and growth and developmental assessments. The schedule should be individualized to your child’s symptoms and medical needs.

Get notified when new evidence is published on Syndromic multisystem autoimmune disease due to Itch deficiency.

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References (6)

1
Biallelic human ITCH variants causing a multisystem disease with dysmorphic features: A second report.
Brittain HK, Feary J, Rosenthal M, et al.
American journal of medical genetics. Part A 2019; (179(7)):1346-1350 doi:10.1002/ajmg.a.61169.
PMID: 31091003
2
Immune Dysregulation in Human ITCH Deficiency Successfully Treated with Hematopoietic Cell Transplantation.
Patel T, Henrickson SE, Moser EK, et al.
The journal of allergy and clinical immunology. In practice 2021; (9(7)):2885-2893.e3 doi:10.1016/j.jaip.2021.04.010.
PMID: 33894394
3
Case Report: Sustained immune and pulmonary recovery three years after hematopoietic stem cell transplantation for ITCH E3 ubiquitin ligase deficiency.
Ashe B, Neal E, Kurland G, et al.
Frontiers in immunology 2026; (17()):1805196 doi:10.3389/fimmu.2026.1805196.
PMID: 42148098
4
Mutation in ITCH Gene Can Cause Syndromic Multisystem Autoimmune Disease With Acute Liver Failure.
Kleine-Eggebrecht N, Staufner C, Kathemann S, et al.
Pediatrics 2019; (143(2)) doi:10.1542/peds.2018-1554.
PMID: 30705142
5
ITCH deficiency clinical phenotype expansion and mitochondrial dysfunction.
Wolfe R, Heiman P, D'Annibale O, et al.
Molecular genetics and metabolism reports 2022; (33()):100932 doi:10.1016/j.ymgmr.2022.100932.
PMID: 36338154
6
ITCH Deficiency Causing Immunodeficiency and Immune Dysregulation.
Hernández A, Cerda C, María Vinet A, et al.
Pediatrics 2025; (156(5)) doi:10.1542/peds.2024-069311.
PMID: 41130596

This page explains possible organ effects and warning signs of ITCH deficiency for informational purposes only and does not constitute medical advice. Your child’s specialist should tailor monitoring and tell you when to seek urgent or emergency care.