BACKGROUND AND OBJECTIVE: Majeed syndrome is an autosomal recessive disorder 
characterised by the triad of chronic recurrent multifocal osteomyelitis, 
congenital dyserythropoietic anaemia and a neutrophilic dermatosis that is 
caused by mutations in LPIN2. Long-term outcome is poor. This is the first 
report detailing the treatment of Majeed syndrome with biological agents and 
demonstrates clinical improvement with IL-1blockade.
METHODS: We describe the clinical presentation, genetic analysis, cytokine 
profiles and response to biological therapy in two brothers with Majeed 
syndrome.
RESULTS: Both boys were homozygous for a novel 2-base pair deletion in LPIN2 
(c.1312_1313delCT; p.Leu438fs+16X), confirming the diagnosis. Their bone disease 
and anaemia were refractory to treatment with corticosteroids. Both siblings had 
elevated proinflammatory cytokines in their serum, including tumour necrosis 
factor α (TNF-α), however a trial of the TNF inhibitor etanercept resulted in no 
improvement. IL-1 inhibition with either a recombinant IL-1 receptor antagonist 
(anakinra) or an anti-IL-1β antibody (canakinumab) resulted in dramatic clinical 
and laboratory improvement.
CONCLUSIONS: The differential response to treatment with TNF-α or IL-1 blocking 
agents sheds light into disease pathogenesis; it supports the hypothesis that 
Majeed syndrome is an IL-1β dependent autoinflammatory disorder, and further 
underscores the importance of IL-1 in sterile bone inflammation.