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

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submitted on 2023-09-26, 06:35 and posted on 2023-10-12, 08:03 authored by Fawzia M. Elgharbawy, Mohammed Yousuf Karim, Dina Sameh Soliman, Amel Siddik Hassan, Anoop Sudarsanan, Ashraf Gad


Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS 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.

Case presentation

We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS 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-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, 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 FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.


We described a new ALPS-FAS clinical phenotype-associated germline FAS 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.



  • English

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License

Institution affiliated with

  • Hamad Medical Corporation
  • Al Wakra Hospital - HMC
  • Hamad General Hospital - HMC
  • Women's Wellness and Research Center - HMC
  • Weill Cornell Medicine - Qatar
  • Sidra Medicine
  • Qatar University
  • Qatar University Health - QU
  • College of Medicine - QU HEALTH

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