Clinical, laboratory, and molecular characteristics of patients with spondyloenchondrodysplasia: a case series study.

Unlabelled: Spondyloenchondrodysplasia (SPENCD) is a rare genetic disorder characterized with skeletal dysplasia, immune dysregulation, and neurological impairment. Patients diagnosed with SPENCD at a single pediatric hematology center were included in the study. The patients' clinical characteristics, symptoms at presentation, imaging and laboratory results, and genetic analysis results were collected retrospectively from their files. This study evaluated nine patients diagnosed with SPENCD, eight of whom had autoimmune manifestations at presentation. Common findings included autoimmune hemolytic anemia, hypothyroidism, and elevated transaminase levels. All patients exhibited short stature and skeletal abnormalities. Neurological symptoms were present in six patients, with intracranial calcifications detected in five. Recurrent bacterial and viral infections, including respiratory tract infections, were prevalent. The NM_001611.5 (ACP5): c.772_790del p.(Ser258TrpfsTer39) frameshift variant was identified in all patients. Two patients died during follow-up.

Conclusion: The study highlights the clinical characteristics and challenges associated with SPENCD. The findings underscore the need for comprehensive management strategies to address the multifaceted complications associated with SPENCD.

What Is Known: • Spondyloenchondrodysplasia (SPENCD) is classified as a type-1 interferonopathy resulting from homozygous mutations in the ACP5 gene, which leads to a deficiency in tartrate-resistant acid phosphatase. • The clinical features associated with this condition encompass skeletal dysplasia, spastic paraparesis, short stature, thrombocytopenia, hemolytic anemia, and systemic lupus erythematosus like autoimmune manifestations. Additionally, patients may experience intracranial calcifications and recurrent infections.

What Is New: • SPENCD exhibits similarities with other type I interferonopathies, including increased levels of type I interferon and specific neurological symptoms; however, it also displays distinct characteristics such as intellectual disability and behaviors associated with autism spectrum disorder. • Despite the rare occurence of the condition and the small number of patients reported here the findings underscore the complexity of managing this condition, particularly in the context of consanguinity and the associated risks of severe complications and mortality.