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Tiago Silva1, José Pedro Vieira2, Teresa Almeida3, Ana Cordeiro1, Marta Conde4, João Farela Neves2

1 Unidade de Imunodeficiências Primárias; 2 Serviço de Neurologia; 3 Unidade de Hematologia, 4 Unidade de Reumatologia, Área de Pediatria Médica; Hospital Dona Estefânia - CHLC EPE. Lisboa – Portugal

V Reunião de Imunodeficiências Primárias. Estoril, 9 de Novembro 2013

Introduction:  TRAP protein (tartrate-resistant acid phosphatase) exists in cells that, despite arising from common myeloid precursors, belong to different systems: musculoskeletal (osteoclasts), nervous (glial cells) and immune (dendritic cells). One of its substrates is osteopontin, a multifunctional protein which has both intra and extra-cellular forms. Changes of TRAP (caused by mutation in the gene ACP5 on chromosome 19), cause a hyperphosphorylation of osteopontin, conditioning a gain of function which results in different clinical manifestations, described in the rare patients with SPENCDI syndrome (spondyloenchondrodysplasia with immune dysregulation, OMIM # 607944). The immunological manifestations are associated uncontrolled production of type 1 IFN.

Case Report: Eighteen year-old female with a history of spastic paraparesis starting at the age of two, disproportionate short stature caused by bone dysplasia (platyspondilia) and systemic lupus erythematosus with difficult to control bicytopenia (autoimmune thrombocytopenia and anemia)and lupus nephritis. The pattern of involvement of three systems (musculoskeletal, immune and neurological), rose the clinical suspition of SPENCDI, later confirmed by ACP5 gene sequencing, which revealed a homozygous mutation in exon 7 (c.791T>A-p.met264.lys).The immunological investigation yeldedno significant alterations.Cytokines assays and characterization of the profile of regulation of IFN-alpha (existence of a "signature interferon alpha”) are ongoing.

Comments: The elucidation of molecular and pathophysiological mechanisms of rare diseases allow not only the expansionof knowledge about the complex mechanisms responsible for the regulation of the immune system, but also the genetic counseling of families and delineation of potential new therapeutic strategies.

Key-words: spondyloenchondrodysplasia, immune dysregulation, SPENCI