[Metabolic disorders in hereditary optic neuropathies]

Area of Science:

• Neurology
• Mitochondrial Diseases
• Nutritional Neuroscience

Background:

• Folate metabolism disorders are implicated in mitochondrial disease pathophysiology.
• Systemic folate deficiency may contribute to mitochondrial folate deficiency.
• Folic acid metabolism is interconnected with vitamin B12 and homocysteine levels.

Purpose of the Study:

• To compare folic acid, vitamin B12, and homocysteine levels in patients with Leber's hereditary optic neuropathy (LHON), autosomal recessive optic neuropathy (ARON), other optic neuropathies, and healthy controls.
• To investigate the association between folate status and hereditary optic neuropathies (HON).

Main Methods:

• Blood serum analysis of folic acid, vitamin B12, and homocysteine.
• Study included 58 patients with LHON/ARON, 49 patients with other optic neuropathies (control), and 20 healthy volunteers (comparison group).

Main Results:

• Patients with HON showed significantly lower folic acid levels (4.0±1.6 ng/mL) compared to controls (p<1.3·10⁻⁸) and comparison groups (p<1·10⁻¹⁷).
• Vitamin B12 levels were significantly lower in HON patients (380.8±168.1 pg/mL) than in the comparison group (p=0.0001).
• Homocysteine levels were significantly higher in HON patients (14.1±5.6 μmol/L) than in control (p=0.0007) and comparison groups (p=0.000003); 75% of HON patients had homocysteine >10 µmol/L.

Conclusions:

• Hereditary optic neuropathies (HON) are associated with decreased folic acid and vitamin B12 levels, and hyperhomocysteinemia.
• Identifying the causes of these metabolic disorders is crucial for understanding folate deficiency's role in HON development.
• Pharmacological treatment targeting folate metabolism may be a potential therapeutic strategy for HON.