Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus

• Published in: Frontiers in pediatrics 2023-04, Vol.11, p.1150179
• Main Authors: Elgharbawy, Fawzia M, Karim, Mohammed Yousuf, Soliman, Dina Sameh, Hassan, Amel Siddik, Sudarsanan, Anoop, Gad, Ashraf
• Format: Article
• Language: English
• Subjects: ALPS (autoimmune lymphoproliferative syndrome); DNT-cells; FAS; newborn; novel variant; Pediatrics; sirolimus
• ISSN: 2296-2360; 2296-2360
• DOI: 10.3389/fped.2023.1150179

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of "double-negative" T-cells (DNTs) (T-cell receptor αβ+ CD4-CD8-) and an increased risk of developing malignancies later in life. We herein report a case of a newborn boy with a novel germline homozygous variant identified in the gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS- . The elder brother of the proband was also affected by ALPS and has been found to have the same homozygous variant associated with a severe clinical phenotype of ALPS- , whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with -related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs. We described a new ALPS- clinical phenotype-associated germline homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms.