Methylation-associated pathways in Macular Telangiectasia Type 2 and ophthalmologic findings in patients with genetic methylation disorders.

Serine (Ser) and glycine (Gly) levels were reported to differ between Macular telangiectasia type 2 (MacTel) patients compared to healthy controls. Since they are closely related to methylation metabolism, this report investigates methylation-associated metabolite (MAM) levels in MacTel patients and retinal changes in monogenetic methylation disorders. Prospective, monocentric study on MacTel patients and healthy controls the underwent a standardized protocol including a blood draw. MAM levels in plasma were determined using targeted quantitative metabolomics. Furthermore, patient records of cystathionine beta-synthase (CBS), methylenetetrahydrofolate reductase (MTHFR), and cobalamin C (MMACHC) deficiency were screened for reported retinal changes. In total, 29 MacTel patients and 27 healthy controls were included. MacTel patients showed lower plasma Ser (p = 0.02 and p = 0.01) and Gly (p= 0.11 and p = 0.11) levels than controls. Principal component analyses revealed that MAM, especially homocysteine, contributed to a distinct clustering of MacTel patients. No retinal changes were seen in CBS (n=1) and MTHFR (n=2) deficiency, while two patients with MMACHC (n=4) deficiency displayed extensive macular dystrophy. MacTel patients show distinct clustering of MAM compared to controls. Of the three homocystinurias, only MMACHC resulted in macular dystrophy, possibly due to distinct compensatory pathways.

Déclaration de conflit d'intérêts

Conflict of interest: No conflicting relationship exists for any author.