Majeed Syndrome

Dr.Jerin.K.John, Dr.Suma Balan (PedRheumat, AIMS), Dr.C. Jayakumar
 
A 7-year-old girl, born at term with a birth weight of 2.5 kg, presented with intermittent bilateral ankle and knee joint pain and swelling since the age of 1 year, along with a past history of skin rash. 
On examination, there was swelling and tenderness of the left ankle and tenderness of the right knee. 
Initial investigations revealed elevated inflammatory markers, including a CRP of 104.88 mg/L, ESR of 47 mm/hr, and a Total Count (TC) of 8.79 x 10^9/L. 
Mild microcytic anemia(Hb 10.5 g/dL, MCV 66.5 fL, MCH 21.0 pg) and thrombocytosis (platelet count 474 x 10^9/L) were also noted. Additional findings included a mildly elevated RDW of 18.2 and normal kidney function with creatinine at 0.5 mg/dL. 
MRI of the affected joints showed short Tau inversion recovery (STIR )bright signals with diffusion restriction involving the right talus, left cuboid, and left navicular bones, suggesting chronic recurrent multifocal osteomyelitis (CRMO). 
Given the lack of response to antibiotics, systemic steroids and methotrexate were initiated, resulting in short-term improvement, but symptom recurrence followed due to non-compliance. Further multisystemevaluation ruled out associated inflammatory conditions, with ophthalmologic screening showing no signs of uveitis and OGD + colonoscopy revealing no gut inflammation. Whole Exome Sequencing (WES) identified mutations in the LPIN2 gene, confirming the diagnosis of Majeed Syndrome.
 
Differential Diagnosis:
1.Juvenile Idiopathic Arthritis (JIA)Considered due to recurrent joint involvement and swelling.  
2.Systemic Lupus Erythematosus (SLE):Included due to systemic inflammation but ruled out based on clinical and lab findings.  
3.Infectious Osteomyelitis:Ruled out due to metaphysealinvolvement and non-response to antibiotics.  
4.Hemoglobinopathies (e.g., Sickle Cell Anemia): Excluded as there were no supportive clinical or laboratory findings, despite the presence of anemia.  
 
The patient was started on NSAIDs and bisphosphonates to manage inflammation and prevent osteoporosis. With clinical improvement achieved, she was discharged with follow-up plans for continued management.
Discussion:
Majeed Syndrome, first reported in children of Arab descent, is a rare autosomal recessive disorder caused mutations in the LPIN2 gene located on chromosome 18. The syndrome is characterized a triad of chronic recurrent multifocal osteomyelitis (CRMO), congenital dyserythropoietic anemia(CDA), and recurrent fevers. Unlike non-syndromic CRMO, this variant may have autoimmune features and shows some response to steroids, highlighting its autoimmune pathogenesis. Although most cases present between the 2nd and 3rd years of life, reports in infancy and adolescence also exist. Laboratory findings are non-specific, with elevated ESR and CRP being the most consistent markers. MRI is the preferred imaging modality, identifying hyperintense lesions with soft tissue involvement. 
 
Management includes NSAIDs, steroids, bisphosphonates, and physiotherapy to maintain mobility and prevent contractures. Targeted biologic therapies such as methotrexate, etanercept (TNF inhibitor), and anakinra (IL-1 receptor antagonist) have shown promising results, with case reports supporting anakinra’s ability to reduce symptoms and inflammatory markers. Agents like infliximab and canakinumab have shown variable outcomes. Given the rarity of the condition, treatment approaches are largely based on case reports. Genetic testing is essential for family counselingand prenatal diagnosis. Prognosis varies, with females with unifocal disease having better outcomes compared to males with multifocal involvement.