title: Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment.
abstract: BACKGROUND
  X-linked Ornithine Transcarbamylase deficiency (OTCD) is often unrecognized in adults, as clinical manifestations are non-specific, often episodic and unmasked by precipitants, and laboratory findings can be normal outside the acute phase. It may thus be associated with significant mortality if not promptly recognized and treated. The aim of this study was to provide clues for recognition of OTCD in adults and analyze the environmental factors that, interacting with OTC gene mutations, might have triggered acute clinical manifestations.
  
  
  METHODS
  We carried out a clinical, biochemical and molecular study on five unrelated adult patients (one female and four males) with late onset OTCD, who presented to the Emergency Department (ED) with initial fatal encephalopathy. The molecular study consisted of OTC gene sequencing in the probands and family members and in silico characterization of the newly detected mutations.
  
  
  RESULTS
  We identified two new, c.119G>T (p.Arg40Leu) and c.314G>A (p.Gly105Glu), and three known OTC mutations. Both new mutations were predicted to cause a structural destabilization, correlating with late onset OTCD. We also identified, among the family members, 8 heterozygous females and 2 hemizygous asymptomatic males. Patients' histories revealed potential environmental triggering factors, including steroid treatment, chemotherapy, diet changes and hormone therapy for in vitro fertilization.
  
  
  CONCLUSIONS
  This report raises awareness of the ED medical staff in considering OTCD in the differential diagnosis of sudden neurological and behavioural disorders associated with hyperammonemia at any age and in both genders. It also widens the knowledge about combined effect of genetic and environmental factors in determining the phenotypic expression of OTCD.
authors.forename: Catia
authors.initials: C
authors.lastname: Cavicchi
authors.forename: Maria
authors.initials: M
authors.lastname: Donati
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Miriam
authors.initials: M
authors.lastname: Rigoldi
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.forename: Francesca
authors.initials: F
authors.lastname: Orfei
authors.forename: Nicolò
authors.initials: N
authors.lastname: Gentiloni Silveri
authors.forename: Aniello
authors.initials: A
authors.lastname: Colasante
authors.forename: Silvia
authors.initials: S
authors.lastname: Funghini
authors.forename: Serena
authors.initials: S
authors.lastname: Catarzi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pasquini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Sean
authors.initials: S
authors.lastname: Mooney
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Amelia
authors.initials: A
authors.lastname: Morrone
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy
chemical_list: D009954:Ornithine Carbamoyltransferase