Combined immunodeficiency due to LCK deficiency

Combined immunodeficiency due to LCK deficiency is an extremely rare primary immunodeficiency disorder caused by biallelic mutations in the LCK gene, which encodes lymphocyte-specific protein tyrosine kinase. LCK plays a critical role in T-cell receptor signaling and T-cell development. This condition is also known as immunodeficiency 22 (IMD22). The disease primarily affects the immune system, leading to severely impaired T-cell function and development, while B-cell and natural killer (NK) cell numbers may be variably affected. Patients typically present in infancy or early childhood with recurrent, severe, and often life-threatening infections, including bacterial, viral, and opportunistic infections. Clinical features may include failure to thrive, chronic diarrhea, skin infections, respiratory infections, and susceptibility to opportunistic pathogens. Laboratory findings characteristically show reduced or absent CD4+ T cells, impaired T-cell proliferation in response to mitogens and antigens, and dysregulated immunoglobulin levels. The T-cell compartment is profoundly affected, with defective thymic T-cell maturation. Treatment is primarily supportive and includes aggressive management of infections with antimicrobial agents, immunoglobulin replacement therapy, and prophylactic antibiotics. Hematopoietic stem cell transplantation (HSCT) represents the only potentially curative treatment option and should be considered early in the disease course. Without definitive treatment, the prognosis is poor due to the severity of immune compromise. Given the extreme rarity of this condition, management is best guided by specialized immunology centers with experience in severe combined immunodeficiency disorders.

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