Liver Dysfunction and Liver Histopathology in Alanyl-tRNA Synthetase 1 (AARS1) Deficiency with a Novel Mutation: A...

Alanyl-tRNA synthetase 1 (AARS1) is a cytosolic enzyme belonging to the Aminoacyl transfer RNA synthetases group that plays a key role in protein translation. Bi-allelic AARS1 mutations presenting as liver dysfunction are rare. A 10-month-old baby girl presented with upper gastrointestinal bleeding and abdominal distension after a short history of febrile illness. There was hepatosplenomegaly with poor growth, microcephaly and delayed developmental milestones on examination. Laboratory investigations showed liver biochemical dysfunction along with correctable coagulopathy. Liver histopathology depicted diffuse macrovesicular steatosis along with expansion of the portal tracts due to accumulation of foamy histiocytes. The hepatic lobules also highlighted the accumulation of foamy histiocytes which were diastase-PAS, faint Perls, and CD68 positive simulating storage cells. Besides, mild portal fibrosis with incomplete septa and mild focal reticulin condensation were also noted. Whole-exome sequencing clinched the diagnosis of a homozygous mutation in the AARS1 gene, a novel mutation with autosomal recessive inheritance. AARS1 mutation affects protein biosynthesis and mitochondrial functions, causing a multisystemic disorder. The first presentation with liver dysfunction is infrequent.