Case report: De novo SAMD9L truncation causes neonatal-onset autoinflammatory syndrome which was successfully treated with hematopoietic stem cell transplantation

Abstract

During recent years, the identification of monogenic mutations that cause sterile inflammation has expanded the spectrum of autoinflammatory diseases, clinical disorders characterized by uncontrolled systemic and organ-specific inflammation that, in some cases, can mirror infectious conditions. Early studies support the concept of innate immune dysregulation with a predominance of myeloid effector cell dysregulation, particularly neutrophils and macrophages, in causing tissue inflammation. However, recent discoveries have shown a complex overlap of features of autoinflammation and/or immunodeficiency contributing to severe disease phenotypes. Here, we describe the first Argentine patient with a newly described frameshift mutation in SAMD9L c.2666delT/p.F889Sfs*2 presenting with a complex phenotypic overlap of CANDLE-like features and severe infection-induced cytopenia and immunodeficiency. The patient underwent a fully matched unrelated HSCT and has since been in inflammatory remission 5 years post-HSCT.

Keywords: CANDLE-like syndrome; SAMD9L; autoinflammatory syndromes; case report; primary immunodeficiencies; sterile alpha motif domain containing 9 like.

Figure 1

First skin lesions: nonevanescent erythematus papular generalized eruption at the first consult 24 days since birth (A), H&E staining showing interstitial infiltrates consisting of some atypical mononuclear cells with karyorrhexis (B), and persistent severe skin ulcers at 2 months of age (C), skin exacerbations previous to anti-TNFα therapy (D), lung MRI showing inflammatory infiltrate at 6 months after the fifth dose of anti-TNFα therapy (E), and skin erythema exacerbation in arms and legs prior to HSCT at 8 months (F).

Figure 2

Plasma levels of IL-6 and IL-8 in HD (n = 5) and the patient before HSCT (black bars) and on day +420 after HSCT (gray bars).