Fragile X-associated tremor/ataxia syndrome with autoimmune hepatitis requiring liver transplantation

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that develops in some carriers of the FMR1 premutation. It starts with slight tremors or unsteadiness that progresses over time and includes cognitive decline. Here, we present the case of a man in his mid-60s with 88 CGG repeats in FMR1 who was diagnosed with FXTAS in his late 50s. In his early 60s, he was diagnosed with autoimmune hepatitis (AIH), confirmed by biopsy, and his liver function declined, requiring a transplant. Recovery was complicated by a bile duct leak, but he eventually stabilised. Neurologically, his symptoms gradually worsened before the transplant; he was falling 7 times a day, showed tremor, ataxia and mild rigidity. MRI demonstrated white matter disease in the middle cerebellar peduncle and the splenium in the corpus callosum. The individual showed improvement in ataxic symptoms after the transplant and is no longer experiencing falls. Although FXTAS is primarily a neurodegenerative disorder, increasing evidence suggests that carriers of the FMR1 premutation are also at higher risk for immune-mediated conditions. However, AIH has not previously been reported in individuals with FXTAS. This suggests a potential broader association between premutation and autoimmune diseases in fragile X premutation carriers. This case highlights the importance of monitoring autoimmune complications in these patients.