Dataset of FADD Deficiency Cases

FADD deficiency is a rare autosomal recessive inborn error of immunity characterized by impaired apoptosis, dysregulated immune activation, and susceptibility to recurrent infections, autoinflammation, lymphoproliferation, and autoimmune manifestations. This dataset was compiled as part of a systematic review analyzing all reported cases of FADD deficiency in the literature. Inclusion criteria encompassed original human clinical studies and non-experimental observational studies, while studies involving non-FADD mutations or in vitro research were excluded. The systematic literature search identified eight relevant articles for review. The reviewed cohort comprised 13 patients. The dataset includes demographic details, genetic findings (FADD gene mutations and inheritance patterns), clinical presentations (fever-related encephalopathy, invasive pneumococcal disease, lymphoproliferation, and organ dysfunction), immunological parameters (lymphocyte apoptosis defects, antibody deficiencies, and double-negative T-cell counts), neuroimaging findings, and treatment outcomes.

Metadata:

• MMR – Measles, Mumps, and Rubella vaccine
• VZV – Varicella-Zoster Virus
• HHV-6 – Human Herpesvirus 6
• CMV – Cytomegalovirus
• EBV – Epstein-Barr Virus
• CT – Computed Tomography
• MRI – Magnetic Resonance Imaging
• IPD – Invasive Pneumococcal Disease (a severe infection caused by Streptococcus pneumoniae, including conditions like meningitis and bacteremia)

The data were extracted from the following sources:

• Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, et al. Whole-exome-sequencing-based discovery of human FADD deficiency. American Journal of Human Genetics. 2010;87(6):873-81.
• Meer E, Solanes F, Kohn L, Kuo CY, Wong DA, Pineles S, et al. Ocular findings associated with FADD deficiency resemble familial exudative vitreoretinopathy. American Journal of Ophthalmology case reports. 2022;25:101305.
• Kohn LA, Long JD, Trope EC, Kuo CY. Novel Compound Heterozygote Variations in FADD Identified to Cause FAS-Associated Protein with Death Domain Deficiency. Journal of Clinical Immunology. 2020;40(4):658-61.
• Vogel B, Boyd NK, Kuo CY, Kohn LA, Soldatos A, Santoro JD. Immunotherapy responsive neuroinflammation in a child with FAS‐associated death‐domain mutation. Clinical Genetics. 2023;103(2):252-3.
• Setia P, Bargir UA, Shanmukhaiah C, Jodhawat N, Gaikwad P, Vedpathak D, et al. Expanding the clinical phenotype of FADD deficiency with a novel mutation and its role in Fas-mediated apoptotic pathway. British Journal of Haematology. 2023;202(2):e11-e5.
• Giovannini G, Giannoccaro MP, Cioclu MC, Orlandi N, Liguori R, Meletti S. FADD gene pathogenic variants causing recurrent febrile infection-related epilepsy syndrome: Case report and literature review. Epilepsia. 2024;65(7):e119-e24.
• Savic S, Parry D, Carter C, Johnson C, Logan C, Gutierrez BM, et al. A new case of Fas-associated death domain protein deficiency and update on treatment outcomes. The Journal of Allergy and Clinical Immunology. 2015;136(2):502-5.e4.