Clinical, pathologic and genetic studies on mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

OBJECTIVE

To study the clinical, pathological and genetic characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

METHODS

Eight cases of MELAS (6 of them were from 2 families) underwent clinical study, muscle biopsy, autopsy on one patient, brain biopsy on one patient and genetic research.

RESULTS

In clinical report the average age of onset was 10-22 years old. Four cases from one family were 3 brothers and their nephew (sister's son). The death age of the three brothers was 16-20 years. Two cases from another family were a brother and a sister. The six patients of the two families showed the typical inherited characters of MELAS. The symptoms were myoclonic epilepsy, stroke-like episodes, paralysis of limbs, progressive mental retardation and neurological deaf. CT showed calcification in globus pallidus and MRI demonstrated clearly the abnormal prolongation of T2-weighed signals that distributed in frontal, parietal, occipital and temporal cortex as multiple focal, cystic and laminar necrotic areas. Pathological studies on brain showed multi-focal, cystic, and laminar or spongy necrotic abnormality primarily in gray matter of frontal, parental, temporal and occipital cortex. Decrease and loss of nerve fibers of the sub-cortical white matters of the lesion areas of cortex and calcification of globus pallidus were also observed. Red ragged fibers (RRF) and abnormal mitochondron were found by muscle biopsies. A point mutation (A-G transition) at nt 4243 in the mitochondrial tRNA Leu (UUR) was confirmed by using PCR and Southern Blot.

CONCLUSION

Although great progress has been made in the clinical, pathological and genetic research of MELAS, the pathogenesis of the disease remains further research.