A case of late‐onset Leber's hereditary optic neuropathy with elevated serum lactic acid and pyruvic acid levels by cycle ergometer exercise

Abstract

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by acute or subacute bilateral vision loss. We describe a female who experienced visual impairment at the age of 75 years. Genetic analysis of peripheral blood leukocytes revealed a point mutation (11778G>A) in MTND4 encoded by mitochondrial DNA. The most distinctive feature of our patient was the elevation of serum LA and PA levels and the LA/PA ratio by cycle ergometer exercise without clinical or pathological skeletal muscle involvement. Also, droplet digital PCR (ddPCR) showed that mutation fractions of m.11778G>A in peripheral blood and muscle sample were higher than 99.9%, indicating “homoplasmy”. Although no cases of LHON with clinical impairment of skeletal muscle have been reported, subclinical mitochondrial dysfunction has been reported. We concluded that the ergometer test sensitively detected a subclinical change caused by mitochondrial respiratory chain dysfunction, showing the diversity of genotype and phenotype relationship in LHON.

Diagnostic Values of Venous Peak Lactate, Lactate-to-pyruvate Ratio, and Fold Increase in Lactate from Baseline in Aerobic Exercise Tests in Patients with Mitochondrial Diseases

“…Patient 6 had Leber-plus disease without muscle weakness and did not show an increase in venous lactate levels during the test. Patients with Leber disease without muscle symptoms have been shown to have either normal ( 37 ) or elevated ( 38 ) venous lactate levels.…”