The Good, The Bad, and The Ugly - Path PPT

Bloodwork showed a normal CBC and BMP. LDL was 128, ESR was 6 mm/hr, and CRP was 0.4 mg/L. A1c was 5.3%, and RPR, FTA-Abs, SPEP, ANA, Rheumatoid Factor, APC-resistance testing, Cardiolipin Abs, and Beta-2 glycoprotein Abs were negative. Ferritin was 202 ng/mL. Leukocyte alpha-galactosidase activity was normal. However, lactate was elevated at 2.6 mmol/L (nl 0.5-1.5), and pyruvate was elevated at 0.10 mmol/L (nl 0.03-0.08), with a Lactate/Pyruvate ratio 26 (nl 10-30). Transesophageal echocardiogram showed normal cardiac function without masses or thrombi. CT angiography of the head and neck revealed no areas of stenosis. Repeat Head CT 6/2014 showed resolution of the previously seen medial occipital lesion, but also a new hypodensity in the posterior frontal lobe, likely correlating with an episode of transient left arm weakness. Given the patient's deficits in vision and hearing, blood was sent for mitochondrial DNA testing for point mutations and deletions, including testing for MELAS, which was negative. Muscle biopsy was also performed, which showed reduced cytochrome oxidase staining in many muscle fibers, but normal mitochondrial enzymatic testing. In addition, there were no fibers with increased staining on succinate dehydrogenase, and no ragged-red fibers on Gomori trichrome. The muscle was subsequently sent for comprehensive mitochondrial genomic analysis by next-generation sequencing, (Baylor test #2085), which revealed a pathogenic 97.7% heteroplasmic 1644G->A point mutation in mitochondrially encoded tRNA valine, confirming the diagnosis of MELAS.