Grand rounds: could occupational exposure to n-hexane and other solvents precipitate visual failure in leber hereditary optic neuropathy?
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.
Carelli
Valerio
V
Dipartimento di Scienze Neurologiche, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
Franceschini
Flavia
F
Venturi
Silvia
S
Barboni
Piero
P
Savini
Giacomo
G
Barbieri
Giuseppe
G
Pirro
Ettore
E
La Morgia
Chiara
C
Valentino
Maria L
ML
Zanardi
Francesca
F
Violante
Francesco S
FS
Mattioli
Stefano
S
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
D000269:Adhesives; D004272:DNA, Mitochondrial; D006586:Hexanes; D012997:Solvents; C026385:n-hexane