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.

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

Stefano Mattioli
Ultimo
Writing – Original Draft Preparation
2007

Abstract

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.
2007
Carelli, Valerio; Franceschini, Flavia; Venturi, Silvia; Barboni, Piero; Savini, Giacomo; Barbieri, Giuseppe; Pirro, Ettore; La Morgia, Chiara; Valentino, Maria L.; Zanardi, Francesca; Violante, Francesco S.; Mattioli, Stefano
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2476901
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