A new case report of autoimmune liver disease in a patient with Noonan syndrome: Risk factors, presentation and management

Background: Noonan syndrome (NS, MIM 163950) is an autosomal dominant multisystem disorder which is included among the RASopathies, and is characterized by short stature, typical facial features and multiorgan involvement. Autoimmune hepatitis is a chronic necroinflammatory disease of the liver, commonly characterized by hypergammaglobulinemia (Ig), circulating autoantibodies, and compatible histological findings (interface hepatitis). The association between Noonan syndrome and susceptibility to autoimmune diseases is known, however only two cases of Noonan syndrome and autoimmune hepatitis have previously been reported. Case presentation: We report the case of a 15-year-old boy with Noonan syndrome due to a mutation in PTPN11 who developed autoimmune hepatitis type 1. The occasional finding of hypertransaminasemia led to the discovery of clinical manifestations such as chronic fatigue and recurrent bouts of headache, the presence of serum antinuclear antibody and borderline smooth muscle antibodies, histological findings (pattern of acute hepatitis with moderate chronic inflammatory infiltrate, neoductulogenesis and ductular metaplasia), and exogenous risk factors. We describe the diagnostic pathway and treatment management (prednisone and azathioprine) and analyze the role of possible co-factors and the rationale behind the therapeutic choice. Conclusion: The liver could be a further target of the immune dysfunction in Noonan syndrome, therefore any signs or symptoms causing suspicion of autoimmune disease require careful evaluation in the management and follow-up of patients with Noonan syndrome and related conditions (RASopathies).