ABSTRACT
The disorder was first described by Shih et al. in a patient with impaired mental development, irritability, and myoclonic spasms, who had intermittent attacks of hyperammonemia and ataxia. The term “hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome” was coined to characterize the specific biochemical pattern that has been observed. The onset of symptoms in HHH syndrome ranges from the neonatal period (=28 days) to late adolescence/adulthood (>12 years). Intermittent episodes of hyperammonemia are characteristic features of this disorder. As in ornithine transcarbamylase deficiency, HHH syndrome may present with a hepatitis-like disease or even fulminant liver failure with severe coagulation abnormalities (e.g. subdural hematoma, gingival bleeding, melena) requiring urgent liver transplantation. Dietary treatment is the essential anchor point of long-term management and requires the knowledge of a specialist metabolic dietitian. A mix of intact dietary protein and medical foods composed of essential amino acids may be necessary.
