Mitochondrial disorders (MD) refer to a clinically heterogeneous group of disorders that arise as a result of a dysfunction of the mitochondrial respiratory chain . They can be caused by either inherited or spontaneous mutations of nuclear (nDNA) or mitochondrial DNA (mtDNA) which lead to altered functions of the proteins or RNA molecules that normally reside in mitochondria. Defects in nDNA can be inherited from either parent, while defects in the genes of the mtDNA are maternally inherited. Mitochondria are present in virtually all cell types of human body, and their damage affects especially the main energy-dependent tissues such as the brain, heart, liver, skeletal muscles, kidney, and the endocrine and respiratory systems [14]. MD primarily affect children, but adult onset is becoming more recognized. Over 100 mtDNA abnormalities associated to MD have been described in the literature, some resulting in profound disability and premature death [15]. Gastrointestinal symptoms are reported in 15 % of patients with MD occurring usually in childhood, before the onset of more classical extraintestinal symptoms of MD [16]. The major MD presenting with GI symptoms are mitochondrial neurogastrointestinal encephalomyopathy (MNGIE ) (peripheral neuropathy, ophthalmoparesis, leukoencephalopathy, muscle wasting, cachexia) [17], Leigh syndrome (subacute necrotizing encephalomyelopathy resulting in hypotonia, bulbar paresis, abnormal eye movements, lack of coordination of extremities, and regressive psychomotor development) [18], Kearns-Sayre syndrome (chronic progressive external ophthalmoplegia, atypical pigmentary retinopathy, ataxia, and heart block) [19], and MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) [20]. MNGIE is a rare autosomal recessive disorder caused by mutations in the gene-encoding thymidine phosphorylase (TP), which lead to absolute or nearly complete loss of its catalytic activity, producing systemic accumulations of its substrates, thymidine (dThd) and deoxyuridine (dUrd) [21]. MNGIE typically presents between the first and third decades with GI symptoms as presenting feature in approximately half of the cases [22]. All patients will eventually develop GI symptoms during the course of the disease. Main symptoms attributable to GI dysmotility include dysphagia, early satiety, nausea, vomiting, abdominal pain and cramps, borborygmi, intestinal pseudo-obstruction, and bloating. These symptoms invariably lead to weight loss, which may manifest as extreme cachexia. Although the average age at presentation is approximately 18 years, GI symptoms have been reported earlier during the first year of life, including diarrhea at 5 months of age in one case and intussusception at 8 months in another infant [22]. Different mtDNA mutations have been associated with GI disorders in MD. Recently Horvath et al. found a new heteroplasmic mutation in the anticodon-stem of mitochondrial tRNA of a girl presenting with clinical symptoms of MNGIE-like GI dysmotility and cachexia [23]. Intestinal pseudo-obstruction is an increasingly recognized clinical feature in MNGIE and represents an important cause of chronic intestinal failure. The pathogenesis of intestinal pseudo-obstruction in MD is still unclear. Giordano et al. described the presence of smooth cell atrophy, mitochondrial proliferation, and mtDNA depletion in the muscularis propria of small intestine in two different studies, performed in one and four patients suffering from MNGIE, respectively [24, 25]. Their pathogenetic hypothesis is that the baseline low abundance of mtDNA molecules may predispose smooth muscle cells of the external layer of muscularis propria to the toxic effects of circulating dThd and dUrd. More recently, Zimmer et al. reported an alteration of the interstitial cells of Cajal (ICC) network in MNGIE [26]. These findings support the hypothesis that ICC loss might be an early pathogenetic event in MNGIE-associated gut motor dysfunction before significant myopathic and/or neuropathic structural changes occur [26]. Poor feeding and vomiting are often the initial presenting symptoms in Leigh syndrome [27, 28]. Mutations in more than 40 mtDNA and nuclear-encoded genes have so far been linked to this condition. Mutations in the nuclear gene-encoding SURF1, a mitochondrial protein involved in cytochrome c oxidase assembly, have been noted in many patients with Leigh syndrome and GI symptoms [29]. Dysphagia is also common in patients affected by Leigh syndrome [30]. Dysphagia seems to be due to primary esophageal dysmotility, neurogenic causes, or a combination of these two factors. Fifteen percent of patients with Kearns-Sayre syndrome, a MD characterized by progressive cytochrome c oxidase deficiency, presents with swallowing difficulties and dysphagia [31]. Shaker et al. described the manometric characteristics of a cervical dysphagia in a patient with Kearns-Sayre observing the absence of pharyngeal peristalsis, abnormally low upper esophageal sphincter resting pressure, and the absence of proximal esophageal peristalsis [32]. Eighty percent of patients with MELAS have the same mtDNA mutation, m.3243A>G, while the remaining cases are caused by a range of other mtDNA mutations. Diagnostic criteria include a stroke-like episode occurring before 40 years, neurological disturbance characterized by seizures and/or progressive dementia, lactic acidosis, and a ragged-red fibers myopathy [33]. Other neurological features include severe migraines, sensorineural hearing loss, peripheral neuropathy, and psychiatric problems including depression. Gastrointestinal problems have been frequently reported in children affected by MELAS. Sproule et al. reported at least one GI disturbance in 64 % of a prospective cohort of 45 patients with a diagnosis of MELAS [34]. Symptoms included abdominal discomfort, vomiting, constipation, diarrhea, gastroparesis, intestinal pseudo-obstruction, and recurrent pancreatitis [34]. Other MD are characterized by nonspecific GI symptoms including dysphagia, delayed gastric emptying, feeding difficulties, GERD and/or vomiting, diarrhea, failure to thrive, and abdominal pain [35]. GI symptoms are predominantly localized in the upper GI tract. Chitkara et al. reported the cases of six children with MD who presented upper GI symptoms such as vomiting, food aversion, poor suck, and feeding intolerance [36]. Dysmotility disorders like delayed gastric emptying and intestinal pseudo-obstruction have been reported in children and adult patients with MD. Gastroparesis has been associated with various diseases and may occur as part of a MD [37, 38]. There is no consensus regarding management of patients with gastroparesis who do not respond to simple antiemetic or prokinetic therapy. Tatekawa et al. proposed a new surgical technique in a 12-year-old girl with pyruvate dehydrogenase complex deficiency with refractory gastroparesis [39].