ClinVar

Verma et al. (1997) described a novel mitochondrial 8313G-A mutation in a boy with prominent gastrointestinal symptoms initially followed by progressive encephaloneuropathy. Development was normal until age 3 when he developed anorexia, episodic vomiting, intermittent abdominal pain with distention, and diarrhea. Intermittent pseudoobstructive GI symptoms and failure to thrive persisted despite attempts at jejunal tube feeding and, later, gastrostomy. At age 7, he developed generalized tonic-clonic seizures followed soon thereafter by frequent myoclonic jerks and progressive mental regression. EEG revealed multifocal spike and slow wave discharges. Between ages 8 and 10, parallel to progressive mental regression and persistent enteric symptoms, he developed cerebellar ataxia, peripheral neuropathy, neural deafness, and pigmentary retinal changes. Plasma lactate was elevated and a muscle biopsy revealed ragged-red fibers lacking cytochrome c oxidase activity and diminished levels of respiratory chain enzyme complexes. A unique SSCP was found in the segment of the mitochondrial chromosome that encompasses the MTTK gene, and direct sequencing of this segment revealed a G-to-A transition at the evolutionarily conserved nucleotide at position 8313. The 8313G-A transition was heteroplasmic in muscle and fibroblasts of the patient, but was absent in white blood cells and platelets from his maternal relatives.