CO2 narcosis as a notable cause of premature death in Nakajo-Nishimura syndrome

Abstract

Nakajo-Nishimura syndrome (NNS) is an inherited inflammatory and wasting disease caused by a distinct homozygous mutation of the PSMB8 gene, which encodes the β5i subunit of the immunoproteasome. Although NNS was originally reported in Japan more than 70 years ago, related diseases with an overlapping entity, namely joint contractures, muscular atrophy, microcytic anemia and panniculitis-associated lipodystrophy (JMP) syndrome and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome, have recently been reported and these three diseases are now collectively referred to as proteasome-associated autoinflammatory syndromes (PRAAS). Although some distinct characteristics can be pointed out in each disease, most patients with these diseases commonly start to show inflammatory attacks in infancy and, after growing-up, clinically resemble progeria with marked emaciation especially in the upper body. Notably, some NNS cases with premature or sudden death have been reported and cardiac failure was considered to be a major cause of death. Here we report a Japanese male case with NNS, who had received no continuous medication and died of CO2 narcosis (respiratory acidosis) triggered by an acute septic infection in the absence of cardiac failure at 47 years of age. Due to a remarkable lipomuscular atrophy and contracture of the chest wall, CO2 narcosis should be noted as an important complication of NNS/PRAAS, which can develop into premature death.