AUTOIMMUNE & INFLAMMATORY NMD: EP.01 Autoimmune necrotizing myopathy with anti-signal recognition particle antibodies in the first year of life

Abstract

Autoimmune necrotizing myopathy with anti-signal recognition particle antibodies (SRP ANM) has been rarely reported in childhood. Case Reports. We report 2 patients with onset in the first years of life. Both received corticosteroids, immunoglobulins, methotrexate, hydroxychloroquine and tacrolimus. Patient 1 has clearly improved. Patient 2 was misdiagnosed as muscular dystrophy for 15 years; nevertheless, after 4 months of therapy there was mild motor improvement. Patient 1. A 6-year-old girl presented with weakness, but her parents could not recall the beginning. She had axial as well as mild to moderate limb girdle weakness. There was no systemic/skin involvement. CK levels were 2.400 UI/l. The DMD MLPA test and next-generation sequencing (NGS) did not reveal any pathogenic mutation. Muscle weakness progressed quickly in the next 3 months, suggesting an acquired myopathy, and SRP antibodies were detected. Muscle biopsy was compatible with ANM. Patient 2. A 4-year-old girl presented with weakness in lower limbs for months. Her family was consanguineous. She achieved ambulation after 18 months. She had proximal limb weakness, as well as scapular winging and calf hypertrophy. Her cognitive capacity was borderline. CK levels were >5.000U/l. MRI disclosed posterior thig involvement and focal edema, but based on the rest of clinical findings, a muscular dystrophy was suspected. Muscle biopsy performed at 5 and 10 years of age showed a dystrophic pattern with necrotic fibers and endomysial connective infiltration. Immunochemistry study for muscular dystrophies was normal. Her clinical course has progressed very slowly. She showed rigid spine and maintains independent walking. At 19 year of age, due to the negativity of the all the genetic tests performed over the time (including NGS), myositis specific autoantibodies were tested and SRP antibodies were positive. Review of the second muscle biopsy disclosed C5b-9 expression in muscle fibers. SRP ANM is under-recognized and consequently undertreated in children. Early diagnosis is crucial to improve outcome.