A NOVEL MITOCHONDRIAL G8313A MUTATION ASSOCIATED WITH PROMINENT INITIAL GASTROINTESTINAL SYMPTOMS AND PROGRESSIVE ENCEPHALONEUROPATHY

We describe a childhood mitochondrial disorder in which the clinical s ymptoms began and remained confined to the gastrointestinal (GI) syste m during the first 4 y. Seizures heralded the onset of progressive enc ephalopathy at age 7, Peripheral neuropathy, retinitis pigmentosa, and neural deafness developed subsequently, Laboratory investigations dis closed elevated levels of plasma lactate, and a muscle biopsy revealed ragged red fibers lacking cytochrome c oxidase activity and diminishe d levels of respiratory chain enzyme complexes. Molecular genetic test s failed to show any of the previously reported pathogenic mitochondri al DNA (mtDNA) mutations, We therefore screened the whole mitochondria l genome by coupling restriction digestions with single-strand conform ational polymorphism (SSCP) patterns. We identified a unique SSCP in t ile segment that encompassed the tRNA(Lys) gene, and direct sequencing of this segment revealed a G --> A transition at an evolutionarily co nserved nucleotide al mtDNA position 8313. This G8313A transition was heteroplasmic in muscle and fibroblasts of the patient, but was absent in the white blood cells and platelets from his maternal relatives. T his report illustrates how GI symptoms can be the initial manifestatio n in a mitochondrial disorder and suggests that mitochondrial dysfunct ion should be considered in differentials of unexplained chronic GI sy mptoms, especially when lactic acidosis or other unrelated clinical si gns or symptoms are present.