LAUSR

W interest, we read the article by Di Nora et al about a 16-year-old male with Kearns-Sayre syndrome (KSS) who underwent heart transplantation (HTX) because of intractable dilated cardiomyopathy. The patient manifested with the 3 cardinal phenotypic features retinopathy, onset <20 years, and progressive external ophthalmoplegia and the additional features short stature and cognitive impairment. The study has a number of shortcomings. The main shortcoming of the study is that the pathogenicity of the variant m.4309G>A has not been proven. Arguments against the pathogenicity of the m.4309G>A variant are that the mutation has not been described previously as pathogenic (the only mtDNA variants associated with KSS include m.3249G>A, m.3255G>A, and 3243A>G), that the heteroplasmy rate was not provided, that no segregation of the variant with the phenotype over generations has been described, that no cybrid or singlefiber studies had been carried out, that no biochemical investigations of the muscle homogenate were carried out, and that no immune-histochemical investigations of the muscle biopsy were provided. On the Yarham-score the variant scores only 1 and is thus not pathogenic. Since mtDNA-related mitochondrial disorders are inherited via the maternal line in 75% of the cases, we should know the family history, particularly if the mother or other first degree relatives were clinically or subclinically affected. Knowing the family history is crucial for assessment of the pathogenicity of the detected mtDNA variant and for genetic counseling. Since KSS is in the majority of the cases due to spontaneous mtDNA deletion, we should be informed if a single mtDNA deletion was excluded in the presented patient. Patients with KSS not only manifest clinically in the central nervous system (ataxia, hypotonia, epilepsy, white matter lesions, cognitive dysfunction), eyes (retinopathy, optic atrophy), muscle (myopathy, lactic acidosis), or heart (subaortic septum hypertrophy, conduction defects) but also in the ears (hypoacusis), endocrine organs (short stature, diabetes, hypopituitarism, hypocorticism, hypothyroidism, hypo-/hyperparathyroidism, hypogonadism), kidneys (renal insufficiency), bone marrow (anemia, thrombocytopenia), or gastrointestinal tract. Frequently, KSS patients present with facial dysmorphism. We should be informed which of these additional features were present in the described patient. Since the reported patient received steroids, mycophenolate mofetil, and cyclosporin, and all these compounds are potentially mitochondrion-toxic, we should know the long-term follow-up, particularly if immunosuppression deteriorated the noncardiac manifestations of the phenotype. KSS or MELAS/KSS overlap syndrome may be associated with left ventricular hypertrabeculation/noncompaction (LVHT). The figure of the explanted heart suggests LVHT. Thus, we should know if LVHT was considered by means of echocardiography or cardiac magnetic resonance imaging before HTX and if the patient ever experienced typical complications of LVHT, such as ventricular arrhythmias, heart failure, or cardio-embolism before HTX. Overall, this interesting report could be more meaningful if the pathogenicity of the described variant was appropriately confirmed, if the family history was provided, if LVHT was excluded or confirmed, and if a long-term follow-up was carried out to assess if mitochondrial disorder patients truly benefit from HTX in the long run.