A patient with typical clinical features of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) but without an obvious genetic cause: a case report

Abstract

Introduction: There are currently 23 missense point mutations and one 4 basepair deletion spanning different mitochondrial genes associated with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The spectrum of mitochondrial DNA mutations in Arab patients with MELAS is largely unknown.

Case presentation: A standard clinical examination was carried out on a 34-year-old Saudi woman showing clinical features of MELAS. Fresh frozen muscle tissue was subjected to enzyme histochemical analysis. DNA was extracted from her leukocytes and muscle tissue, and the full mitochondrial genome was screened for base substitution mutations and deletions. Additionally, we screened the polymerase gamma-1 nuclear gene for mutations. The patient was negative for the most common m.3243 A>G MELAS mutation. Sequencing the full mitochondrial genome did not reveal any known or potentially pathogenic sequence changes. The polymerase gamma-1 gene was also free from mutations.

Conclusion: The clinical picture described here typically fits that observed in patients with MELAS or mitochondrial stroke-like events, but mutations in recognized genes (mitochondrial DNA and polymerase gamma-1 gene) were absent. We report the case of a patient with typical clinical features of MELAS, but without an obvious genetic cause.

Figure 1

(a) A computed tomography brain scan showing bilateral basal ganglia calcification; the cerebellum shows prominent folia indicating mild cerebellar atrophy. (b) Axial T2 brain magnetic resonance image scan showing left temporo-parieto occipital ischemic lesion. (c) Axial T2 brain magnetic resonance image scan showing the extension of the parietal temporal region to the occipital lobe, and also showing a right occipital lesion. (d) Magnetic resonance spectroscopy showing inversion of J-coupling phenomenon at 1.3 ppm, indicating lactate peak.

Figure 2

(a) Modified Gomori trichrome stain showing several ragged red fibers (arrowhead). (b) Cytochrome c oxidase stain showing Type-1 lightly stained and Type II fibers, darker fibers, and a few fibers with abnormal collections of mitochondria (arrowhead). Note cytochrome c oxidase negative fibers as usually seen in mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). (c) Succinate dehydrogenase staining showing a few ragged blue fibers and intense staining in the mitochondria of the blood vessels (arrow). (d) Electron microscopy showing abnormal collection of mitochondria with paracrystalline inclusions (arrowhead), osmiophilic inclusions (large arrowhead) and mitochondrial vacuoles (small arrowhead).