TUBB3 E410K syndrome with childhood-onset non-alcoholic steatohepatitis.

Context Nonalcoholic fatty liver disease (NAFLD) is becoming a major issue worldwide, even in children. Multiple parallel hits hypothesis has been suggested as progress of NAFLD, but the mechanism of NAFLD is not completely understood. β-Tubulin is essential in mitoses, neuronal migration, and axon guidance during neuronal development. Pathogenic variants in the TUBB3 gene were shown to be associated with a wide spectrum of neurological abnormalities, but not accompanied with hepatic complications, such as NAFLD. Case description A 11-year-old girl has been followed up as atypical Moebius syndrome since infancy, as she was born with bilateral ptosis, paralytic strabismus, and facial weakness. At the age of 7 years, she was diagnosed with TUBB3 E410K syndrome by whole exome sequencing. At the age of 10 years, her blood examination revealed elevated liver transaminase levels, which persisted for almost 2 years. She underwent liver biopsy, the results of which was suggestive of non-alcoholic steatohepatitis (NASH). The expression of TUBB3 was absent, but that of tyrosine hydroxylase (TH) was present in the parenchymal nerve fibers of the liver. On the other hand, in comparison with an autopsy case of NASH and a normal control, these showed co-expression of TUBB3 and TH in the liver. Conclusion We report the first case of TUBB3 E410K syndrome accompanied with NASH. This case suggests that TUBB3 mutation may be associated with the pathogenesis and progression of NASH in humans.