Nakajo syndrome

Nakajo syndrome, also called nodular erythema with digital changes or Nakajo-Nishimura syndrome, is a rare inherited disorder first reported in 1939 by A. Nakajo in the children of parents who were blood relatives. It follows an autosomal recessive pattern: a child is affected only after receiving a faulty copy of the PSMB8 gene, which sits on chromosome 6 and helps build the immunoproteasome, a protein-recycling complex of immune cells. Signs begin in early childhood with red, swollen lumps on the skin that worsen in cold weather, repeated fevers, and long fingers and toes with clubbed tips. Joint pain and contractures follow, mostly in the hands, wrists and elbows, together with progressive loss of muscle and body fat that leaves the face, chest and arms very thin. Some people also have an enlarged liver and spleen, anaemia, low platelet counts, calcification in the basal ganglia and intellectual disability. Diagnosis rests on a set of clinical criteria and is confirmed by finding a disease-causing variant of the gene. There is no cure; steroids may reduce inflammation, but the loss of fat continues despite treatment. The condition overlaps with other PSMB8-related autoinflammatory syndromes, and some researchers regard them as forms of one disease.