title: HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation.
abstract: We report a 3-year-old Italian patient with the hyperornithinaemia, hyperammonaemia, homocitrullinuria (HHH) syndrome who presented with neurological deterioration after an intercurrent infection. Hyperammonaemia, coagulopathy and moderate hypertransaminasaemia were detected on hospital admission. Severe hepatocellular necrosis with hypertransaminasaemia (aspartate aminotransferase 20,000 UI/L, alanine aminotransferase 18,400 UI/L) and coagulopathy (PT < 5%) rapidly developed within few days, prompting evaluation for liver transplantation. A protein-restricted diet and arginine supplementation were immediately started, with a rapid improvement of the patient's neurological conditions and normalization of liver function tests and blood ammonia. The diagnosis of HHH syndrome was based on the presence of the typical metabolic abnormalities. Molecular analysis of the SLC25A15 gene showed that the patient was heterozygous for two novel mutations (G113C and M273K). The diagnosis of HHH syndrome should be considered in patients with fulminant hepatitis-like presentations. Early identification and treatment of these patients can be life-saving and can avoid liver transplantation.
authors.affiliation: Department of Pediatrics, Federico II University, Via S Pansini 5, 80131 Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Fecarotta
authors.forename: G
authors.initials: G
authors.lastname: Parenti
authors.forename: P
authors.initials: P
authors.lastname: Vajro
authors.forename: A
authors.initials: A
authors.lastname: Zuppaldi
authors.forename: R
authors.initials: R
authors.lastname: Della Casa
authors.forename: M T
authors.initials: MT
authors.lastname: Carbone
authors.forename: A
authors.initials: A
authors.lastname: Correra
authors.forename: G
authors.initials: G
authors.lastname: Torre
authors.forename: S
authors.initials: S
authors.lastname: Riva
authors.forename: C
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: G
authors.initials: G
authors.lastname: Andria
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D026923:Amino Acid Transport Systems, Basic; D001120:Arginine / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D002675:Child, Preschool; D002956:Citrulline / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D018753:Diet, Protein-Restricted; D006505:Hepatitis / Q000175:diagnosis*; D006801:Humans; D022124:Hyperammonemia / Q000150:complications* / Q000175:diagnosis; D008099:Liver / Q000473:pathology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000175:diagnosis; D033681:Mitochondrial Membrane Transport Proteins; D009952:Ornithine / Q000097:blood / Q000652:urine*; D011506:Proteins / Q000235:genetics; D013577:Syndrome
chemical_list: D026923:Amino Acid Transport Systems, Basic; D033681:Mitochondrial Membrane Transport Proteins; D011506:Proteins; C442901:SLC25A15 protein, human; C001352:homocitrulline; D002956:Citrulline; D001120:Arginine; D009952:Ornithine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase