LETTER TO THE EDITOR
We disagree with the diagnosis of MIDD [Hiruma, T. et al., 2023]. MIDD is characterised by diabetes and deafness alone, but the index patient also suffered from dilated cardiomyopathy, renal insufficiency, hepatopathy, and presumably short stature (BMI: 15.6kg/m2). Therefore, the diagnosis should be changed to MIDD plus or non-syndromic mitochondrial disorder. MIDD plus is common and can occasionally be associated with dilated cardiomyopathy or heart failure [Seiler, F. et al., 2023]. In addition to diabetes, hypoacusis, and cardiomyopathy, the index patient presented also with hepatopathy (elevated transaminases), renal insufficiency, and short stature. Prospective instrumental studies are required to evaluate the patient for subclinical involvement of the brain, endocrine organs, and eyes, Serum and cerebrospinal fluid lactate should be measured. In this context, the HbA1c value at admission is also missing to assess whether the diabetes was well controlled and whether the renal failure was due to diabetic nephropathy or a true phenotypic manifestation of the mutation. Kidney involvement is common in m.3243A>G carriers [Di Toro, A. et al., 2022]. It should also be clarified whether elevated liver transaminases were due to liver congestion due to right heart failure, to muscle involvement, or to the mutation.
A second point to discuss is that heteroplasmy rates of the m.3243A>G variant have not been reported in any of the clinically affected tissues (e.g. myocardium). Knowledge of mutational load is crucial as it can determine disease progression and is essential for genetic counselling. There is also no mention whether the mtDNA copy number was normal or reduced and which haplotype the patient belonged to.
The third point to discuss is that sitagliptin has not been considered a cause of heart failure. Sitagliptin has been found to increase the risk of congestive heart failure, particularly at high doses or in renal failure, as in the index case, [Muanda, F. T. et al., 2020]. A meta-analysis reported that DPP-4 inhibitors generally cause sympathetic activation as a class effect and therefore increase the risk of heart failure [Sano, M, 2019].
It should also be explained what was the rationale for administering taurine in such a high dose. The standard daily dose is 1000mg/d. Overall, the study has limitations which challenge the results’ interpretation. Addressing these limitations could further strengthen and reinforce the statement of the study. Although transcatheter edge-to-edge repair with the MitraClip system seems to be a viable approach to treating mitral valve regurgitation, the underlying cause of mitral insufficiency, left ventricular heart failure, should also be optimally treated. This includes discontinuing any regularly administered medications that could potentially worsen heart failure