ITCH Deficiency Causing Immunodeficiency and Immune Dysregulation

Area of Science:

• Genetics
• Immunology
• Pediatrics

Background:

• Itchy E3 Ubiquitin Protein Ligase (ITCH) deficiency is an extremely rare autosomal recessive disorder.
• It results from ITCH gene alterations, leading to immunodeficiency and systemic autoimmunity.
• Clinical manifestations can be severe and multi-systemic.

Purpose of the Study:

• To report a case of ITCH deficiency in a pediatric patient.
• To describe the clinical presentation and genetic findings.
• To emphasize the importance of considering this rare condition in differential diagnoses.

Main Methods:

• Case report of a 12-year-old girl.
• Clinical examination and laboratory analysis including lymphocyte subpopulations.
• Genetic testing for ITCH gene variants.
• Imaging studies (chest CT scan).

Main Results:

• The patient presented with chronic malnutrition, short stature, dysmorphic features, global developmental delay, and intellectual disability.
• She exhibited chronic lung damage, exocrine pancreatic insufficiency, immune-mediated diabetes mellitus, hypothyroidism, and hypoparathyroidism.
• Genetic testing identified a homozygous splice donor variant (c.1569+1G>T) in the ITCH gene.

Conclusions:

• ITCH deficiency, even with rare variants like c.1569+1G>T, can lead to severe multi-systemic complications.
• Early recognition and consideration of ITCH deficiency are crucial for managing patients with combined immunodeficiency and autoimmunity.
• This case underscores the potentially life-threatening nature of ITCH deficiency.