ND2 mutation with minimal coenzyme-Q responsive manifestations.

Letter to the Editor,

With interest we read the article by Zanolini et al. about a 21 yo male with exercise-intolerance since age 7 y, recurrent vomiting since age 17 y, muscle wasting, decreased tendon reflexes, high-arched palate and mal-occlusion detected at age 20 y, exercise-induced supraventricular tachycardia, and lactic acidosis due to a ND2 mutation [1]. The patient profited from coenzyme-Q [1]. We have the following comments and concerns.

We do not regard retinitis pigmentosa, polyneuropathy and hypoacusis as central nervous system features, as mentioned in the introduction. Additionally, there was not only muscle but also gastro-intestinal and cardiac involvement.

Mitochondrial vomiting is a frequent phenotypic feature of MELAS [2] and cyclic vomiting syndrome [3]. However, vomiting has been also reported in patients carrying SUCLA2, POLG1, TWINKLE, ETFDH, or tRNA(Trp) mutations, and in patients with combined complex-I,III,IV deficiency, MNGIE, KSS, Leigh-syndrome, Leigh-like syndrome, MERRF/MELAS overlap syndrome, depletion syndrome, pyruvate-dehydrogenase deficiency, Pearson syndrome, or non-specific syndromic mitochondrial disorder. Was vomiting in the presented patient associated with headache or migraine-like attacks? Which were the results of gastroscopy? Did vomiting respond to coenzyme-Q? Which other therapy was applied?

The patient is reported to have cardiac involvement [1]. Did he also undergo cardiac MRI with contrast medium to look for noncompaction and late gadolinium enhancement? Did supraventricular tachycardia respond to low-dose coenzyme-Q? Did he require antiarrhythmic treatment?

A number of patients with a MID may profit from adherence to a ketogenic diet [4]. Was the patient recommended to take a low-glycemic diet? [5]

The ND2 mutation obviously occurred spontaneously [1]. Which was the cause? Was the mutation load below the detection limit in the other family members of the maternal lineage? Was there no biological relationship between the proband and other family members?

Overall, this interesting case evokes questions, which should be addressed to further strengthen the report and to learn more about the phenotypic and genotypic peculiarities of MIDs.