Assessment and Prevalence of Gastrointestinal Dysfunction in Children With Mitochondrial Disorders (MD)

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.