Non‐alcoholic steatohepatitis in a child with cartilage‐hair hypoplasia syndrome

Abstract

We report an unusual pediatric case of cartilage‐hair hypoplasia (CHH) characterized by significantly impaired cellular immunity, recurrent sinopulmonary infections, severe non‐alcoholic steatohepatitis (NASH) and terminal liver failure. A 14‐year‐old boy was diagnosed clinically with CHH by age 1 year. His childhood was complicated by recurrent otitis media, bronchiectasis, and sinopulmonary infections due to bacteria and rare mold including Chaetomium. Immunological testing revealed absolute CD4 and CD8 count depletion. The diagnosis of CHH was confirmed by RNase mitochondrial RNA‐processing (RMRP) gene testing, which demonstrated not only the typical mutation at position c70 but an additional atypical mutation at position c213. By age 14, he had a 3‐year history of NASH. A diagnostic work‐up could not demonstrate any common etiologies for fatty liver including infectious,autoimmune, mitochondrial or metabolic etiologies. The terminal events of this child's life included hepatic failure and Chaetomium pneumonia. NASH involves the inability of hepatocytes to clear fat vesicles. CHH is largely a disorder of cellular proliferation. RMRP functions in mitochondrial DNA synthesis and in cleaving pre‐rRNA. This example of NASH with CHH raises the issue of whether the second, atypical mutation identified may be related to progressive liver disease, and whether the RMRP gene may have additional, currently unrecognized functions related to insulin resistance, liver metabolism or cellular immunity.