Spondyloenchondrodysplasia Q77.7

Rare autosomal-dominantly inherited autoinflammatory disease (genetic skeletal dysplasia) which is classified as a type 1 interferonopathy. Type 1 interferonopathies represent a group of rare, genetically and phenotypically heterogeneous disease patterns caused by a malfunction of the innate immune system (Crow YJ 2011). With the exception of multifactorial SLE, these are very rare diseases, and type 1 interferonopathies are pathogenetically based on disorders in the metabolism and in the immunological recognition of intracellular nucleic acids.

Spondyloenchondrodysplasia is caused by mutations in the ACP5 gene encoding tartrate-resistant acid phosphatase 5 (Lausch E et al. 2011); Briggs TA et al. 2011). The enzyme dephosphorylates and inactivates osteopontin, which on the one hand promotes bone resorption in osteoclasts and on the other hand has a stimulating effect on the type I interferon axis in dendritic cells.

Clinically, spondyloenchondrodysplasia is characterized by skeletal dysplasia, which is characterized by small growth, enchondromas in the tubular bones or in the pelvis. SPENCD may have a heterogeneous clinical spectrum with neurological involvement (spasticity, intelligence impairment and cerebral calcifications) or autoimmune manifestations such as immune-thrombocytopenic purpura, systemic lupus erythematosus (hemolytic anemia and thyroiditis). Recurrent infections may also occur.

1. Briggs TA et al (2011) Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet 43:127-131
2. Lausch E et al (2011) Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity. Nat Genet 43:132-137