Definition:

Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an autosomal recessive skeletal dysplasia, characterised by radiolucent metaphyseal and vertebral lesions. Patients may exhibit varying degrees of neurological impairment including spasticity, developmental delay, and basal ganglia calcification. In addition, signs of autoimmune disease resembling systemic lupus erythematosus (SLE) are commonly observed. Furthermore, patients may also suffer from recurrent infections. SPENCD is caused by biallelic mutations in ACP5, encoding tartrate-resistant acid phosphatase (TRAP). Affected individuals displayed an absence of TRAP serum expression and, in keeping with autoimmune manifestations, increased levels of serum interferon-alpha (IFNalpha) and an upregulation of interferon-stimulated genes (ISGs).