Phenotypic and Genotypic Characteristics and Damage Accrual of Monogenic Autoinflammatory Diseases other than Familial Mediterranean Fever from the Pediatric Rheumatology Arab Group (PRAG)

Objective: To report the phenotype, genotype and response to treatment in Arab children with monogenic autoinflammatory diseases (AIDs) other FMF, with focus on accrual damage.

Methods: We retrospectively reviewed patients with clinical and/ or genetically proven monogenic AIDs other than FMF seen between 1990 and 2018 at 10 rheumatology clinics from seven Arab countries. Data were collected at the last follow- up visit comprising consanguinity, age at onset and diagnosis, clinical and laboratory findings, treatment, damage accrual and death related to monogenic AIDs.

Results: Seventy (46 female) patients with monogenic AIDs were analyzed. Consanguinity rate was 74.6% and a family history of AIDs was present in 60%. The mean age at disease onset was 3.2±2 years. The initial diagnosis was inaccurate in 47% and the mean diagnosis delay was 4±3 years. The most frequent monogenic AIDs were LACC1 associated monogenic JIA and monogenic Crohn’s (23) followed by CAPS (12), TRAPS (12), HIDS (9), Majeed’s syndrome (6). Musculoskeletal involvement was the main feature in LACC1 associated monogenic disorders. Genetic testing was performed in 67 patients, 69% had genetically confirmed disease. Patients with mutation c.T850C p.C284R in exon 4 of LACC1 had severe arthritic changes. Three CAPS patients with NLRP3 mutation had cognitive impairment and one with significant hearing and ocular damage. Two HIDS patients had homozygous p.V3771 mutation and other two patients with p.V3771/compound heterozygous MEFV: p.E148Q/p.P369S/p.R408G. Three different LPIN2 mutations were recorded for Majeed’s syndrome. Overall, growth failure was the most frequent (36%), followed by cognitive impairment (13%). There were three deaths due to infection.

Conclusion: The number of genetically confirmed patients with monogenic AIDs other than FMF are not uncommon among Arab children probably due to a high consanguinity rate. Diagnostic delay and high damage accrual emphasize the need for more awareness and early referral to specialized centers.