Autor(es): Costa e Castro, A ; Maia, R ; Batalha, S ; Freixo, JP ; Martins, C ; Neves, C ; Cordeiro, AI ; Neves, JF
Data: 2022
Identificador Persistente: http://hdl.handle.net/10400.17/4212
Origem: Repositório do Centro Hospitalar de Lisboa Central, EPE
Assunto(s): Bone Marrow/failure; Hypopigmentation; Immunodeficiency; Ligase iv; Lymphopenia; HDE PED; HDE HEM PED
DNA ligase IV deficiency is a rare autosomal recessive disorder associated with impaired DNA repair mechanisms. Most patients with DNA repair defects present with neurologic deficits, combined immunodeficiency, bone marrow failure, and/or hematologic neoplasia. We present 3 unrelated cases of ligase IV deficiency with different clinical presentations. Patient 1 presented at the age of 5 with bone marrow failure, dysmorphic features, and T and B lymphopenia. A compound heterozygous variant L19W/K635fs in the LIG4 gene was identified. Patient 2 presented at the age of 16 with recurrent infections. He had agammaglobulinemia and absent B cells. A homozygous R278H in the LIG4 gene was identified. Patient 3 was referred for vitiligo and B-cell lymphopenia (low class-switched B cells) and hypogammaglobulinemia. Homozygous R278H in LIG4 was also identified. In the last few years, the spectrum of clinical manifestations caused by ligase IV deficiency has widened, making it very difficult to establish an accurate clinical diagnosis. The use of NGS allows a proper diagnosis and provides a better prognosis and adequate family counseling.
