Spondyloenchondrodysplasia

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized by the combination of vertebral abnormalities (platyspondyly) and enchondroma-like radiolucent lesions in the metaphyses of long bones. The disease is caused by biallelic pathogenic variants in the ACP5 gene, which encodes tartrate-resistant acid phosphatase (TRAP). This enzyme deficiency leads to accumulation of osteopontin, which affects both skeletal development and immune regulation. SPENCD affects multiple body systems, most notably the skeletal system and the immune system. Skeletal features include short stature, platyspondyly (flattened vertebral bodies), irregular metaphyseal lesions resembling enchondromas, and coxa vara. Many patients also develop significant neurological and immunological complications, including intracranial calcifications, spasticity, and autoimmune manifestations such as systemic lupus erythematosus (SLE), autoimmune hemolytic anemia, thrombocytopenia, and thyroiditis. Some patients may also exhibit intellectual disability. The clinical spectrum of SPENCD is broad, ranging from predominantly skeletal disease to severe multisystem involvement with prominent autoimmunity and neurological impairment. The condition is sometimes referred to as spondyloenchondrodysplasia with immune dysregulation (SPENCDI, OMIM #607944). Diagnosis is based on characteristic radiographic findings combined with biochemical evidence of low serum TRAP activity and genetic confirmation of ACP5 mutations. There is no specific curative treatment for SPENCD. Management is supportive and multidisciplinary, involving orthopedic care for skeletal complications, immunosuppressive therapy for autoimmune manifestations, and neurological monitoring. Growth hormone therapy has been considered in some cases of short stature, and standard treatments for lupus-like autoimmune disease are employed when indicated.

Common questions about Spondyloenchondrodysplasia