Mitochondrial diseases (MD) are a clinically, biochemically and genetic heterogeneous group of disorders caused by mutations in genes that encode proteins involved in mitochondrial function. Neuropathy, ataxia, and retinitis pigmentosa (NARP) and Leigh syndrome (LS) are both established mitochondrial syndromes; sometimes the clinical manifestations in these diseases may overlap. LS is defined as an early-onset progressive neurodegenerative MD typically characterized by subacute onset of psychomotor regression and encephalopathy associated with the development of bilateral symmetrical lesions in the basal ganglia, thalami, subthalamic regions, mesencephalon, and brainstem, which are the hallmarks of the disease. In contrast, NARP is another mitochondrial syndrome characterized by sensory axonal neuropathy, ataxia, retinitis pigmentosa, epileptic seizures, cognitive impairment, sensorineural hearing loss, diabetes mellitus, and cardiomyopathy. Our patients manifested with recurrent seizures, muscle weakness, psychomotor retardation, feeding difficulties, elevated lactate and alanine; meanwhile, additional symptoms include exercise intolerance and partial atrophy of the optic nerve in the case of the patient with NARP syndrome, as well as tremor, ataxia and abnormal ECG in the patient with LS. Considering the multisystemic impairment and the presence of predominantly neurological clinical manifestations, an underlying mitochondrial respiratory chain disorder was suspected taking into account the clinical phenotype of the patients, and confirmed by biochemical, instrumental and genetic examinations. Evaluating the clinical criteria for mitochondrial diagnosis according to the Nijmegen Mitochondrial Disease Criteria Scale, there were counted 8 points for both patients as scoring for definite mitochondrial disorder. The first-line investigations used in this case of inborn error of metabolism indicated elevated lactate in blood [2.2-2.4 mmol/L (LS) and 3.7-7.8 mmol/L (NARP); ref. val. 0.7-2.1 mmol/L], hyperalaninemia Ala [594 μmol/L (LS) and 1038 μmol/L (NARP), ref. val. <450 μmol/L], Ala/ Lys ratio [3.44 (LS) and 11.8 (NARP), abnormal if >3] and hyperaminoaciduria. Neuroimaging findings consisted of pathological foci in the bilateral basal nuclei in the case of NARP, and a symmetrical distribution of lesions along thalamus, mesencephalon, brainstem, medullary tegmentum and cerebellar hemispheres (periventricular) and medulla oblongata, in a pattern that is characteristic of LS. Genetic analysis revealed the m.3243A>G mutation in the MT-TL1 gene in the case of the patient with LS and in the patient with NARP syndrome the m.8993T>G mutation was identified in the MT-ATP6 gene of the mitochondrial genome. Early onset in the presence of complete health, the polymorphism of clinical manifestations, such as a central nervous system lesion, muscle weakness, impaired psychomotor development, and seizures in a child should prompt the clinician to consider a mitochondrial disorder namely LS or NARP, and conduct further investigations such as measurement of blood lactate, magnetic resonance imaging, and if possible, genetic analysis.