A rare case of late-onset spondyloenchondrodysplasia with immune dysregulation presenting as adult-onset monogenic lupus.

Abstract

Spondyloenchondrodysplasia is classified as an interferonopathy resulting from recessive mutations in the ACP5 gene and manifests with various clinical features, including distinctive skeletal dysplasia, neurological abnormalities, immune dysfunction resembling systemic lupus erythematosus (SLE) and Sjogren's syndrome. While SLE is typically considered multifactorial and more prevalent in adulthood, a subset of approximately 10%-25% of childhood cases arise from monogenic form. Among these, spondyloenchondrodysplasia accounts for only a rare fraction of monogenic lupus cases, with only 22 reported instances in the literature. This paper presents a new case of spondyloenchondrodysplasia-immune dysregulation (SPENCDI) in an adult patient born to nonconsanguineous parents. The patient was diagnosed with SPENCDI and exhibited immune neutropenia, anti-dsDNA positivity, platyspondyly, immune deficiency, and a homozygous variant (c.155A > C, p. Lys52Thr) in the ACP5 gene, previously classified as pathogenic. Notably, the patient achieved successful clinical management through the initiation of baricitinib treatment, a Janus kinase inhibitor. SPENCDI represents an uncommon cause of SLE in adulthood. Clinicians should be vigilant of underlying Mendelian inheritance when encountering patients with associated features. While treatments for both Mendelian and non-Mendelian SLE are similar, Janus kinase inhibitors like baricitinib show potential for managing interferon-signature monogenic SLE cases.