Progressive increase of serum zinc level in a Pediatric patient with PSTPIP1- p.N236K mutation.

BACKGROUND: Mutations of the cytoskeletal protein proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) are associated with a spectrum of rare autoinflammatory disorders, including PAPA (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) and PAMI (PSTPIP1-associated myeloid-related inflammatory) syndromes, characterized by various dermatologic and hematologic abnormalities. Mechanistically, this has been linked to an increased affinity for pyrin, leading to autoinflammation and caspase-1 activation. We present a case report of a rare missense PSTPIP1 variant not previously associated with clinically significant findings.

CASE REPORT AND RESULTS: The patient is a full-term Caucasian male who presented shortly after birth with pancytopenia in the setting of presumed bacterial meningitis. Whole genome sequencing identified a c.708C > G, p.N236K missense mutation in PSTPIP1, which is not present in the population database gnomAD. A similar c.708C > A, p.N236K variant is classified as being of uncertain significance on ClinVar (Variation ID: 1022810) based on a single submission, but is not currently linked to PAMI syndrome. This patient further demonstrated a progressive increase in serum zinc concentrations and autoinflammation markers.

CONCLUSION: This case report provides support for other pathogenic PSTPIP1 mutations associated with PAMI syndrome with a progressive increase in zinc and autoinflammation biomarkers. Furthermore, it addresses difficulties in establishing the diagnosis. It emphasizes the utility of molecular testing when faced with inexplicable clinical presentations and the need for an integrated diagnostic algorithm for PAMI.