Two genetic disorders (TRMU and SCYL1) explaining transient infantile liver failure in one patient

Abstract

Introduction: Paediatric acute liver failure (PALF) has an extremely heterogeneous aetiology, with some genetic disorders being associated with recurrent/transient episodes of infantile hepatopathy. Here, we report a patient who experienced a severe episode of liver failure with complete recovery, and in whom were discovered two genetic disorders possibly explaining this occurrence: a mitochondrial disease caused by pathogenic variants in TRMU gene and the CALFAN syndrome secondary to mutations in SCYL1 gene. Case presentation: Healthy female child who was admitted at hospital by the age of 13 months due to acute hepatic failure in context of febrile flu. Hepatotropic infectious diseases were excluded and metabolic evaluation was normal, with exception of positive allopurinol testing. Liver biopsies revealed focal ballooning of hepatocytes and pronounced fibrosis. The liver function gradually recovered. From age of 3 years, she developed intention tremor, and after the age of 10 progressive ataxia and motor-sensory neuropathy. She is now 25 years-old and presents a cerebellar syndrome, without cognitive impairment. There were no further episodes of hepatic failure and serial evaluation showed normal liver function, without evidence of important fibrosis in transient elastography. Genetic analysis revealed that the patient has two novel variants in heterozygosity in TRMU gene, and, in homozygosity, an already known pathogenic variant in SCYL1 gene. Conclusion: Although patient presents neurological features of CALFAN syndrome, it is discussed which genetic disorder (SCYL1 or TRMU) was responsible for the acute liver failure episode.