Exercise-induced Falls Attributed to the Variant m.8344A>G.

To the Editor We read with interest the article by Miyaue et al. regarding a 42-year-old man with exercise-induced falls that were attributed to weakness and wasting of the right quadriceps femoris muscle (1). The patient carried the variant m.8344A>G with a heteroplasmy rate of 94% in the muscle (1). We have several comments and concerns regarding this article.

We do not agree that this patient should be diagnosed with MERRF. The term “MERRF” describes a clinical syndrome with canonical features of ataxia, myoclonus, generalised epilepsy, and ragged-red fiber (RRF) myopathy (2). Additional features can include exercise intolerance, lipomatosis, ptosis, myalgia, hearing loss, heart disease, migraine, cognitive impairment, diabetes, neuropathy, and CK elevation. There are also a number of overlapping cases of different specific mitochondrial syndromes, such as MERRF/MELAS, MERRF/CPEO, MERRF/Leigh syndrome, MERRF/NARP, and MERRF/KSS. Given that the present patient had no myoclonus, generalised epilepsy, or ataxia, he cannot be diagnosed with MERRF. At most, he can be characterised as having abortive MERRF syndrome.

Despite the attempt to explain the exercise-induced falls in the index patient, the cause of this abnormality remains obscure. Whether the exercise-induced falls are truly attributable to unilateral quadriceps femoris weakness remains speculative, and other explanations for this phenomenon should be considered. Did the authors consider cardiac involvement? Were pro-BNP, long-term ECG, or echocardiography findings normal? Was the Schallong-test normal? Was carotid ultrasound indicative of a stenosis? The authors should also clarify if the patient underwent neurological investigations immediately after the falls. Was there muscular hypotonia or any reduced tendon reflexes? Were laboratory investigations carried out after the falls? Was acute metabolic acidosis due to lactic acidosis induced by exercise present? Metabolic acidosis may be an explanation, given the abnormal lactate stress test. Even CSF-lactate can increase upon exercise (3).

Concerning the transmission of the mutation it would be interesting to know if the patient's mother or other first-degree relatives were neurologically investigated, if they presented with any features indicative of a mitochondrial disorder, and if any of them carried the tRNA(Lys) variant. Carriers of the variant may be asymptomatic (4) and need to be prospectively investigated for MERRF or MERRF plus.

In summary, this interesting case does not meet the clinical criteria for a MERRF diagnosis. Attributing recurrent exercise-induced falls to weakness and wasting of the quadriceps femoris muscle is justified only after the exclusion of other possible causes.

The author states that he has no Conflict of Interest (COI).