title: Grand rounds: could occupational exposure to n-hexane and other solvents precipitate visual failure in leber hereditary optic neuropathy?
abstract: BACKGROUND
  Leber hereditary optic neuropathy (LHON) is a maternally inherited loss of central vision related to pathogenic mutations in the mitochondrial genome, which are a necessary but not sufficient condition to develop the disease. Investigation of precipitating environmental/occupational (and additional genetic) factors could be relevant for prevention.
  
  
  METHODS
  After a 6-month period of occupational exposure to n-hexane and other organic solvents, a 27-year-old man (a moderate smoker) developed an optic neuropathy. The patient had a full ophthalmologic and neurologic investigation, including standardized cycloergometer test for serum lactic acid levels and a skeletal muscle biopsy. His exposure history was also detailed, and he underwent genetic testing for LHON mitochondrial DNA mutations. The patient suffered a sequential optic neuropathy with the hallmarks of LHON and tested positive for the homoplasmic 11778G--> A/ND4 mutation. Routine laboratory monitoring revealed increased concentrations of urinary 2.5 hexandione (n-hexane metabolite) and hippuric acid (toluene metabolite) in the period immediately preceding the visual loss.
  
  
  CONCLUSIONS
  In a subject carrying an LHON mutation, the strict temporal sequence of prolonged appreciable occupational exposure followed by sudden onset of visual loss must raise a suspicion of causality (with a possible further interaction with tobacco smoke).
  
  
  CONCLUSIONS
  In this article, we add to the candidate occupational/environmental triggers of LHON and highlight the need for appropriate case-control (and laboratory) studies to validate the causal effect of mixed toxic exposures.
authors: Dipartimento di Scienze Neurologiche, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors: Valerio
authors: V
authors: Carelli
authors: Flavia
authors: F
authors: Franceschini
authors: Silvia
authors: S
authors: Venturi
authors: Piero
authors: P
authors: Barboni
authors: Giacomo
authors: G
authors: Savini
authors: Giuseppe
authors: G
authors: Barbieri
authors: Ettore
authors: E
authors: Pirro
authors: Chiara
authors: C
authors: La Morgia
authors: Maria L
authors: ML
authors: Valentino
authors: Francesca
authors: F
authors: Zanardi
authors: Francesco S
authors: FS
authors: Violante
authors: Stefano
authors: S
authors: Mattioli
mesh_terms: D000269:Adhesives; D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics; D006586:Hexanes / Q000633:toxicity*; D006801:Humans; D008297:Male; D009154:Mutation; D016273:Occupational Exposure / Q000009:adverse effects*; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis* / Q000235:genetics; D012997:Solvents / Q000633:toxicity*; D015354:Vision, Low / Q000209:etiology
chemical_list: D000269:Adhesives; D004272:DNA, Mitochondrial; D006586:Hexanes; D012997:Solvents; C026385:n-hexane