Gastrointestinal Dysfunction in Children Affected With Mitochondrial Disorders
Condition: Gastrointestinal Dysfunction; Mitochondrial Disorders
MeSH terms: Mitochondrial Diseases
Study type: Observational

Summary: 
      Hypothesis: Many patients with underlying mitochondrial disorders have feeding problems
      because of poor gastrointestinal motility; feeding problems lead to growth impairment and
      many affected children are malnourished.
    

Detailed description: 
      Specific AIM: To study gastric emptying times in children with mitochondrial disorders.

      INTRODUCTION: Mitochondrial disorders are a recently described group of metabolic disorders
      with complex presentations; children present with a myriad of symptoms and involvement of a
      wide array of organ systems. Mitochondrial disorders result from dysfunction of proteins or
      ribosomes utilized by mitochondria. Mitochondrial dysfunction causes a lack of ATP production
      and without enough ATP cells are unable to perform their biological functions.

      The first mitochondrial disease was described in 1962. Over the last 40 years, mitochondrial
      disease has become increasingly recognized as an important group of genetic disorders. The
      prevalence has been reported to be as high as one in 3000 children, approaching that of
      childhood cancer. Mitochondrial disorders have classically been described as affecting
      tissues with the highest demand for ATP, i.e., brain, muscles, nerves, heart, and liver.
      Increasing diagnosis of patients with mitochondrial disease has led to expansion of the known
      spectrum of systemic involvement. Many children with mitochondrial disorders have
      gastrointestinal manifestations, predominately constipation and poor gastrointestinal
      motility. Poor motility effects feeding and many of these patients are intolerant to oral
      feeding and require mechanical feeding to survive.

      Currently there are no proven treatment strategies for children with mitochondrial disorders.
      Most of the current management strategies are nonspecific and target symptom control with
      only limited utility and success.

      Study Methods: We plan to conduct a large, prospective cohort study of 25 children with
      mitochondrial disorders. Subjects will include children with different subclasses of various
      mitochondrial disease subgroups who meet the modified Walker criteria for diagnosis of a
      probable or definite mitochondrial disorder.

      Gastric emptying times will be measured to assess gastrointestinal motility, function, and
      dynamics.

      Research Design and Methods: Participants for this study will be recruited prospectively
      through the University of Texas (UT) Mitochondrial Clinic. All mitochondrial patients with
      probable or definite mitochondrial disorders from 3 to 18 years of age seen at the University
      of Texas Mitochondrial Clinic will be invited to participate. The decision to participate or
      not to participate in this research study will in no way affect medical care offered by
      clinicians involved in the UT Mitochondrial Clinic.

      Consent for study participation will be obtained by the Principal Investigator (PI) or
      co-investigator (CI) or designated clinical nurse in person and a copy of the signed consent
      form will be retained on file by the PI, placed in the patient's research medical record
      (separate from the clinic record). For minor participation (12 to 17 years) parental
      permission and consent of the child will be obtained. For minor participation (7 to 11 years)
      parental permission and assent of the child will be obtained. For minor participation (birth
      to 6 years), parental permission will be obtained

      This study population consists of a cohort of patients with different subsets of
      mitochondrial disorders, including children with isolated deficiencies of the electron
      transport chain and children with syndromic mitochondrial disorders. Final analysis will will
      evaluate results both individually and in subclass groups, ie, Complex I deficiency, MELAS
      (mitochondrial encephalopathy lactic acidosis and stroke-like syndrome), etc.

      Research design: Patients will undergo testing for gastric emptying scans at our radiology
      department. The studies would be performed using Technetium-99 as tracer by our UT
      radiologist David Wan, MD. Patient would report on the morning of the study NPO and would
      drink the tracer. The transit of the contrast material through the stomach would be monitored
      and evaluated with regularly scheduled X Rays of the stomach and the final results would be
      interpreted as normal, delayed or significantly delayed.

      Risks and Benefits : The risks of this study are largely confined to maintaining patient
      confidentiality. There will be no personal benefit to the participant/family. No payment will
      be offered in exchange for study participation. Successful development of a patient database
      will provide valuable information on the natural history of these complicated disorders.

      Information derived from the database will be published in a peer reviewed medical journal;
      however no individual would be identified and all personal information would be kept
      confidential. A potential benefit to the scientific community will be greater understanding
      of the clinical course and expected laboratory values observed in persons with mitochondrial
      disease. There are no foreseeable risks to the research staff.

      Confidentiality: All participants' names and other information will be kept strictly
      confidential. All participants will be assigned a subject ID number and an individual
      identification number. The code linking name and subject ID number will be maintained in a
      locked file in the office of the PI and in a spread sheet file on the office computer of the
      PI. All subsequent reference to patient data will be in anonymous form by patient
      identification number.

      Determine if gastric emptying times in children with mitochondrial disorders are abnormal.

      There are no known risks of performing gastric emptying scan studies in children.

      The risk of allergy to eggs/food is similar to that observed in other children of similar age
      groups and is minimal.

      RISKS:

      Risk associated with the allergic reaction to the dye is also similar to the one observed in
      other children of similar age groups and is minimal.

      Risk associated with breach of confidentiality- minimal. The names and other identification
      information pertinent to the patient's identity and test results would be strictly kept
      confidential and patients would be never identified by their names or other pieces of
      information in public or to anyone else not related to the study.

      Patient's test results would also be not released to the insuring companies directly or
      indirectly.

      Risk associated with the procedure- The procedure itself is very safe and has been performed
      in children of all age groups including the ones suffering from chronic disorders like the
      mitochondrial disorders all the time. Our radiologists are familiar with the nature of
      medical disorder that these children presents with and are very comfortable performing this
      procedure in a safe and timely manner.
    

Intervention name(s): gastric emptying scan
Intervention type(s): Procedure
Intervention description(s): subjects will eat a solid meal (scrambled eggs, etc) or drink liquid (water or juice) mixed with approximately 0.5 millicuries of radioactive material. A scanner/external gamma camera will be placed over the subject's stomach at 15 minute intervals for a duration of 90 minutes (monitoring the amount of radioactivity in the stomach). As the radioactively-labeled food empties from the stomach, the amount of radioactivity in the stomach decreases. The rate at which the radioactivity leaves the stomach reflects the rate at which food is emptying from the stomach. The radioisotope has a half life of approximately. 6 hours and is totally eliminated from the body within 24 hours.
In subjects with gastroparesis, the food and the attached radioactive material remain in the stomach longer than normal (usually hours) before emptying into the small intestine. As a result, the scanner continues to show radioactivity in the area of the stomach for hours after the test meal.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        children suffering form mitochondrial disorders.
      
Keywords: subjects suffering from mitochondrial disorders with one or more gastrointestinal symptoms would be the focus of the study