MELAS

Our pediatric grand rounds topic last week was MELAS syndrome, a mitochondrial genetic disorder characterized by neurological and muscular symptoms like ataxia and fatigue, respectively. MELAS is an acronym for: mitochondrial encephalomyopathy, lactic acidosis, stroke-like symptoms. As with typical mitochondrial inheritance patterns, MELAS is passed maternally (from mother to children), although rare cases of new mitochondrial mutations have been documented.

Since this was a pediatric neurology conference, the treatment course was discussed in the context of the brain. Impaired vasodilation in intracerebral vessels has been linked to brain damage. How do we increase blood flow to prevent said damage? With the potent vasodilator, nitric oxide (NO), of course. As a biochemistry major in undergrad, metabolic pathways always appealed to me. “Oh, ‘X’ becomes ‘Y’ which becomes ‘Z’ which is shuttled inside the organelle and phosphorylated to ‘Z-P’ and…” blah blah blah. A nightmare, right? 😉

The figure above illustrates how our body normally synthesizes nitric oxide. Of interest, according to the speaker, L-citrulline is more efficacious than L-arginine in producing a vasodilatory effect – both substrates are included in the pathway above. Patients are currently started on regimens of L-arginine, but perhaps in the future, L-citrulline will become the mainstay as more evidence emerges.