Improvement of cardiomyopathy after ketogenic diet in a patient with Leigh syndrome caused by MTND5 mutation

Abstract

BackgroundMitochondrial diseases (MDs) are heterogeneous group of disorders caused by inborn defects in the mitochondrial respiratory chain (MRC) and malfunctions of cellular oxidative phosphorylation (OXPHOS). MDs are caused by mutations both in mitochondrial and nuclear DNA. Leigh syndrome (LS) is a neurodegenerative MD with specific clinical and neuroradiological features. There is a broad clinical spectrum of MDs, including organ-specific and multiorgan presentations with symptoms occurring at any age. High energy requiring organs are most frequently involved and cardiac involvement is common. At present there is no specific treatment for MD. Ketogenic diet (KD) has been proposed as a treatment option for patients with MD with seizures or myopathy. It is suggested that KD itself may trigger cardiological complications after long-term therapy, but according to an animal model study, KD could be considered as a therapeutic option for some mitochondrial cardiomyopathies.MethodHere we present a retrospective case report on a male infant diagnosed with LS (m.12706T > C in MTND5) with severe progressive hypertrophic cardiomyopathy, with significant cardiological improvement after KD implementation .ResultsThe ketogenic diet was introduced in a male infant with clinical, biochemical and radiological features of Leigh syndrome, confirmed by next-generation sequencing (NGS) (known pathogenic variant in mtDNA), suffering from severe progressive hypertrophic cardiomyopathy and heart failure with no significant improvement on cardiological treatment, mitochondrial cocktail therapy and mechanical ventilation. The follow-up after KD initiation have shown significant clinical improvement in cardiovascular efficiency and echocardiographic parameters with no adverse effect observed so far.ConclusionScreening for cardiomyopathy is a standard of care (SoC) in the management of patients with mitochondrial disease. Although there are reports suggesting the efficacy and safety of KD in patients with mitochondrial disease, more studies are needed to understand the pathophysiology of mitochondrial diseases and to determine which patients are likely to benefit from this therapy.

Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital

“…Facilitated by the size of our molecularly defined cohort, we were able to expand the phenotype associations of SURF1, report further significant associations for MT-ATP6, MT-ND5, and PDHA1, and report 42 additional potential, although none significant, associations which may in the future be confirmed in a sufficiently powered study (see Table 2 Table S4). The importance of these findings for recognition of disease is exemplified by cardiomyopathy, reported in 6 of 11 patients with MT-ND5 defects, previously only reported in a single patient among a cohort of 20 patients with MT-ND5 defects 38 and a number of case reports, 39,40 where implementation of preventative measures and anticipatory care in routine clinical practice would be beneficial (eg, echocardiogram surveillance). 41 As required for the diagnosis of LS, all patients displayed characteristic bilateral lesions in the basal ganglia (77%) or brainstem (73%), or both (49%) on MRI and/or DWI, in addition to less frequently reported neuroradiological abnormalities, such as cerebral atrophy (34%), white matter involvement (19%), and cerebellar lesions (17%).…”