Non-producer multiple myeloma presenting with acute hyperammonemic encephalopathy: case report

Hyperammonemic encephalopathy (HE) is a rare and life-threatening complication of multiple myeloma, with underlying mechanisms that are not fully understood. In contrast to previously reported cases, most of which have been associated with IgG or IgA isotypes, we describe a patient with HE as the presenting symptom of non-producer multiple myeloma (NPMM).

A 60-year-old man developed lethargy that progressed into coma. He was found to have an elevated ammonia level, despite normal hepatic function. He was diagnosed with HE secondary to NPMM, demonstrating 80% plasma cells without light chain expression in the bone marrow and absence of a monoclonal protein in the serum or urine, including by matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MASS-FIX). Myeloma-directed therapy with daratumumab, bortezomib, cyclophosphamide and dexamethasone successfully reversed his HE. At clinical relapse, he received salvage chemotherapy followed by venetoclax therapy, leading to a short period of neurological recovery.

This case demonstrates that HE can occur in a patient with NPMM and challenges the mechanism suggested by limited prior studies; i.e., that excess ammonia in multiple myeloma arises from degradation of M-proteins. We postulate that the neoplastic plasma cells in NPMM have amplified amino acid metabolism, despite lacking detectable intracellular or secreted immunoglobulins.