Experience with Phosphoryl Transferase Inhibition in Subacute Necrotizing Encephalomyelopathy

Cooper, Joel; Pincus, Jonathan H.; Itokawa, Yoshinori; Piros, Katalin

doi:10.1056/nejm197010082831506

Cited by 56 publications

(10 citation statements)

References 5 publications

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“…The present findings do not exclude a role of thiamine triphosphate in the ethiology of the neuropathologic findings as observed in Leigh's disease [3,4]. The maintainance of the pyruvate dehydrogenase complex in its active form, as demonstrated here, is, however, an effect of the thiamine administration.…”

Section: Discussioncontrasting

confidence: 86%

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The Effect of Thiamine Treatment on the Activity of Pyruvate Dehydrogenase: Relation to the Treatment of Leigh's Encephalomyelopathy

1973

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ExtractRats received intraperitoneal injection of thiamine (125 mg'/kg body wt) for 4 consecutive days. There was less inhibition by ATP (9% ± 2%) of the pyruvate dehydrogenase complex of isolated liver mitochondria from treated rats than in liver mitochondria from control rats (30% ± 8%). The liver mitochondria of the treated animals contained about 25% more thiamine pyrophosphate than the mitochondria of the controls (0.48 ± 0.03 and 0.36 ± 0.01 nmoles/mg mitochondrial protein, respectively) .Roche and Reed have demonstrated inhibition of the phosphorylation of the pyruvate dehydrogenase complex by thiamine pyrophosphate, thereby maintaining pyruvate dehydrogenase in the active form. It is suggested that the therapeutic effect of high doses of thiamine given to patients who suffer from Leigh's disease is, at least in part, due to maintainance of the pyruvate dehydrogenase complex in its active form, thus facilitating the oxidation of pyruvate. Speculation

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Section: Discussioncontrasting

confidence: 86%

“…Mitochondrial extracts were prepared with 18% HC1O 4 , followed by neutralization with 30% KHCO 3 . After standing for 1 hr at 0° the mixture was centrifuged and the supernatant analyzed for thiamine phosphates as described by Cooper et al [3].…”

Section: Methodsmentioning

confidence: 99%

The Effect of Thiamine Treatment on the Activity of Pyruvate Dehydrogenase: Relation to the Treatment of Leigh's Encephalomyelopathy

1973

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“…Pincus and co-workers [6,20] described the presence of the inhibitor of adenosine triphosphate-thiamine diphosphate (ATP-TDP) phosphoryltransferase in the urine of patients with SNE. However the proportion of false positives and false negatives has increased as experience has grown.…”

Section: Discussionmentioning

confidence: 99%

Biochemical study in 28 children with lactic acidosis, in relation to Leigh's encephalomyelopathy

et al. 1985

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An enzymatic study of cultured skin fibroblasts was made in 28 patients with lactic acidosis. In three of these patients a diagnosis of Leigh's encephalomyelopathy was established from autopsy findings. Pyruvate decarboxylase (PDC) deficiency was found in four patients. In two of them, in whom Leigh's encephalomyelopathy was proved by autopsy, PDC activity was lower than 10% of the normal. The other two living patients, who showed 22%-25% of the normal activity, had clinical symptoms and courses different from Leigh's disease. These findings suggest that the patients with severe PDC deficiency develop Leigh's disease but those with mild deficiency may not. A deficiency of cytochrome c oxidase was found in two siblings. One of them, who was diagnosed as having Leigh's encephalomyelopathy by postmortem examination, showed a reduction of cytochrome c oxidase in the liver and brain. In the other sibling, who is living, the reduction of cytochrome c oxidase was demonstrated in the cultured skin fibroblasts and biopsied muscle. In an electron-microscopic study of biopsied muscle, two patients with mitochondrial myopathy were found. Their fundamental enzymatic defects were unclear. In two patients, in whom Leigh's disease was suspected following a brain CT, the production of 14CO2 from [3-14C] pyruvate was found to be low; suggesting a reduced activity of the TCA cycle. In another 18 patients, the fundamental defect was not clear.

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“…How ever, a deficiency of thiamine triphosphate was found in the brains of children who died from infantile Leigh's disease (Cooperetal, \969\Mur-phy et al, 1974). Furthermore, an inhibitor of the enzyme ATP-thiamine pyrophosphate phos photransferase, responsible for the synthesis of thiamine triphosphate, is present in the urine and the body fluids of such patients (Cooper et al, 1970;Pincus et al, 1973;Pincus, 1972;Murphy et al, 1974). These biochemical find ings are difficult to evaluate at present, but may well be related to the pathogenesis of the disease.…”

Section: Discussionmentioning

confidence: 99%

Subacute Necrotizing Encephalopathy (Leigh) in an Adult

Ulrich¹,

Fankhauser-Mauri²

1978

Eur Neurol

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The case of a 31-year-old man who died after a 4 month illness of adult subacute necrotizing encephalomyelopathy (Leigh) is reported. The disease presented with visual disturbances and the principal symptoms were ptosis, a conjugate ophthalmoparesis and a slight tremor of the hands. The case was misdiagnosed as probable multiple sclerosis. Neuropathology disclosed characteristic symmetrical necrotizing lesions, mainly localized in the brain stem. The similarity of the lesions with Wernicke’s disease is pointed out. Possible etiological and pathogenetic factors are discussed.

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Experience with Phosphoryl Transferase Inhibition in Subacute Necrotizing Encephalomyelopathy

Cited by 56 publications

References 5 publications

The Effect of Thiamine Treatment on the Activity of Pyruvate Dehydrogenase: Relation to the Treatment of Leigh's Encephalomyelopathy

The Effect of Thiamine Treatment on the Activity of Pyruvate Dehydrogenase: Relation to the Treatment of Leigh's Encephalomyelopathy

Biochemical study in 28 children with lactic acidosis, in relation to Leigh's encephalomyelopathy

Subacute Necrotizing Encephalopathy (Leigh) in an Adult

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