Digestive Dysmotility in Mitochondrial Neurogastrointestinal Encephalomyopathy

Study Overview
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Brief Summary
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Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an ultra-rare mitochondrial disease caused by mutations of the gen that codifies the enzyme thymidine phosphorylase The genetic defect results in systemic accumulation of the nucleosides thymidine and deoxyuridine. Clinically MNGIE is characterized by a combination of gastrointestinal and neurological manifestations, including severe gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia and sensorimotor neuropathy. Gastrointestinal symptoms are the most frequent first manifestation of the disease, and include early satiety, nausea, dysphagia, postprandial emesis, abdominal pain, abdominal distention, and diarrhea. The disease is relentlessly progressive and the cause of death is primarily related to digestive dysmotility. However, the specific motor dysfunctions that produce the symptoms, i.e., the underlying mechanisms, remain uncertain.

Detailed Description
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Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an ultra-rare mitochondrial disease caused by mutations of the gen that codifies the enzyme thymidine phosphorylase The genetic defect results in systemic accumulation of the nucleosides thymidine and deoxyuridine. Clinically MNGIE is characterized by a combination of gastrointestinal and neurological manifestations, including severe gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia and sensorimotor neuropathy. Gastrointestinal symptoms are the most frequent first manifestation of the disease, and include early satiety, nausea, dysphagia, postprandial emesis, abdominal pain, abdominal distention, and diarrhea. The disease is relentlessly progressive and the cause of death is primarily related to digestive dysmotility. However, the specific motor dysfunctions that produce the symptoms, i.e., the underlying mechanisms, remain uncertain, because so far, no studies on gastrointestinal motility in MNGIE have been published. The aims of this study were to identify the upper GI motor dysfunction in MNGIE patients, and to determine their relation to the clinical manifestations. Since the life-threatening consequences of the disease involve the upper gastrointestinal tract, all patients, after a thorough clinical and neurological evaluation, fulfilled a structured clinical questionnaire on digestive manifestations, and underwent state-of-the-art evaluation of the esophagus and the small bowel by high-resolution manometry (HRM), and gastric emptying by scintigraphy

Official Title
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Enteric Dysmotility in Mitochondrial Neurogastrointestinal Encephalomyopathy Patients Detected by High-resolution

Conditions
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MNGIE, Dysmotility

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of MNGIE disease established by thymidine phosphorylase activity and mitochondrial mutation analysis.
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intestinal motility at diagnosis | to assess the number of intestinal contractions (contractions per minute) during fasting and after the infusion of nutrients measured by high-resolution intestinal manometry | In patients included, in the first 30 days from diagnosis | 
| intestinal motility at diagnosis | to assess the amplitude (mmHg) of contractions during fasting and after nutrients measured by high-resolution intestinal manometry | In patients included, in the first 30 days from diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intestinal motility response to hepatic transplant | to assess changes in the number of intestinal contractions (contractions per minute) during fasting and after the infusion of nutrients measured by high-resolution intestinal manometry after hepatic transplant | one and two years after hepatic transplant treatment | 
| intestinal motility response to hepatic transplant | to assess the amplitude of intestinal contractions during fasting and after the infusion of Amplitude (mmHg) of contractions during fasting and after nutrients measured by high-resolution intestinal manometry after hepatic transplant | one and two years after hepatic transplant treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intestinal manometry, motility