Spondyloenchondrodysplasia Due to Mutation in ACP5 Gene Presenting with Nephrotic Syndrome: A Case Report

Abstract

AbstractSpondyloenchondrodysplasia (SPENCD) with immune dysregulation (SPENCDI) is a rare autosomal recessive inherited immuno-osseous dysplasia characterized by spondylo-metaphyseal enchondromas, along with immune dysregulation ranging from immunodeficiency to autoimmune disorder. Here, we present two cousins with ACP5 gene mutation who had severe short stature with mild hypogammaglobulinemia, nephrotic syndrome, autoimmune thyroiditis and cerebral calcification (Case 1); and in the other (Case 2), there was no clinical findings other than severe short stature, CD4+−T cell lymphopenia and non-autoimmune compensated hypothyroidism. We wanted to emphasize that monogenic causes should be considered in the etiology of early-onset nephrotic syndrome due to the detection of a mutation in the ACP5 gene (her actual diagnosis was changed to SPENCDI.) 5 years after the diagnosis of nephrotic syndrome in the first case, and that the renal involvement may occur without SLE in patients with ACP5 mutation. Severe short stature was a common finding in both cases. We underlined that the clinic can be different even in the same mutation, due to the absence of cerebral calcification and renal involvement in the second case, which is a cousin with Case 1. As a result, endocrinologists, immunologists, rheumatologists, nephrologists and orthopedists should be aware of this syndrome, because SPENCDI causes a pleiotropic (due to more than one phenotypic effect of a gene) clinical picture. Severe short stature may be the only presenting sign of patients with SPENCDI. In addition, in the presence of early-onset nephrotic syndrome and autoimmune thyroiditis, the patient should be evaluated for this type of monogenic disorders as well.