Grand rounds: could occupational exposure to n-hexane and other solvents precipitate visual failure in leber hereditary optic neuropathy?

Environ Health Perspect. 2007 Jan;115(1):113-5. doi: 10.1289/ehp.9245.


Context: 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.

Case presentation: 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.

Discussion: 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).

Relevance: 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.

MeSH terms

  • Adhesives
  • Adult
  • DNA, Mitochondrial / genetics
  • Hexanes / toxicity*
  • Humans
  • Male
  • Mutation
  • Occupational Exposure / adverse effects*
  • Optic Atrophy, Hereditary, Leber / diagnosis*
  • Optic Atrophy, Hereditary, Leber / genetics
  • Solvents / toxicity*
  • Vision, Low / etiology


  • Adhesives
  • DNA, Mitochondrial
  • Hexanes
  • Solvents
  • n-hexane