ABSTRACT
Methionine adenosyltransferase I/III deficiency, also known as Mudd's disease, is a rare inborn error of methionine metabolism. Because pathophysiological mechanisms of the disease remain poorly understood, the consequences of this disorder and the need for medical management remain uncertain; likewise, the effect of medical interventions on clinical outcomes in Mudd's disease is largely unknown due to a relative lack of published longitudinal clinical data. There are few reports of adults in the medical literature affected with this disease. Clinical symptoms of reported adults range from asymptomatic to individuals with neurological, developmental, or behavioral symptoms. Here we report three siblings affected with Mudd's disease that were ascertained following an abnormal newborn screen for hypermethioninemia in the case of our index patient. All three had a variable degree of longstanding neurologic or psychiatric symptoms which had not prompted a clinical investigation for a genetic or metabolic disorder prior to identification through our clinic. While the causal association of these symptoms to the metabolic disorder remains unclear in these cases, all three patients demonstrated a degree of amelioration of symptoms and/or improvement in measurements on standardized psychiatric ratings scales when specific therapy for the metabolic disorder was instituted. The symptoms, treatment, and outcomes over the course of six years of follow-up are presented here, expanding the possible natural history of Mudd's disease.