Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with acanthocytosis: a clinicopathological study of a unique case

Abstract

A case of a unique combination of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like syndrome (MELAS) with acanthocytosis is reported. Neuropathological examination revealed pellagra-like change in Betz cells, brain-stem neurons and anterior horn cells as well as findings compatible with mitochondrial encephalomyopathies. Abnormal function of nicotinic acid-related enzymes could be the cause of the complicated clinicopathologic findings in this case. This is the first report of MELAS with acanthocytosis.

Oxidative Phosphorylation Diseases

“…In a number of cases of MERRF and MELAS, symptoms are combined in the same patient (Shapira et al, 1975;Kuriyama et al, 1984;Kuriyama and Igata, 1985;Mukoyama et al, 1986;Fukuhara, 1985;Lach et al, 1986). In one patient with MERRF+SE, mtDNA analysis revealed a homoplasmic 400-bp deletion in the Complex I subunit gene ND5 (Saifuddin Noer et al, 1988).…”

“…The absence of strokelike episodes appears to differentiate MERRF from MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) (Pavlakis et al, 1984). A difficulty in classification arises when patients with myoclonic epilepsy, mitochondrial myopathy, and dementia develop strokelike episodes later in their clinical course (Shapira et al, 1975;Kuriyama et al, 1984;Kuriyama and lgata, 1985;Mukoyama et al, 1986;Fukuhara, 1985;Lach et al, 1986). Some of these cases may represent small mtDNA deletions and are therefore distinct from MERRF (see Class III mutations: mtDNA deletions and duplications (Saifuddin Noer et al, 1988).…”

“…While most cases of MELAS are spontaneous occurrences within the pedigree (lchiki et al, 1988;Yoda et al, 1984;Kobayashi et al, 1982Kobayashi et al, , 1986Kobayashi et al, , 1987bGoda et al, 1987a,b;Hasuo et al, 1987;Mukoyama et al, 1986;Pavlakis et al, 1984;Bogousslavsky et al, 1982;Hayes et al, 1985;M. Yamamoto et al, 1987;Berkovic et al, 1987a), several informative pedigrees have characteristics that are compatible with an mtDNA mutation.…”

Neuropathology and pathogenesis of mitochondrial diseases

“…This condition is characterized by multiple focal necrotic lesions of varying extent and age. These are always present in the cerebral cortex but may also occur in the cerebral white matter, cerebellum, brainstem, thalamus and basal ganglia (Shapira et al 1975;Kuriyama et al 1984;Mukoyama et al 1986;Ihara et al 1989;Mizukami et al 1992). Although the lesions resemble areas of infarction, they do not follow vascular territories.…”

“…Although the lesions resemble areas of infarction, they do not follow vascular territories. Areas of calcification are also a major feature of the MELAS syndrome, with deposits particularly in the basal ganglia but sometimes also in the thalamus, cerebellum and midbrain (Shapira et at 1975;Hart et al 1977;Kuriyama et al 1984;Mukoyama et al 1986;Ohama et al 1987). In addition to these lesions, there is often some degree of spongiform degeneration in the cortex and neuronal loss in the cortex and cerebellum (Hart et al 1977;Mukoyama et al 1986;Ohama et al 1987;Kishi et al 1988).…”