Leigh's subacute necrotizing encephalopathy: clinical and biochemical study, with special reference to therapy with lipoate.

A defect in pyruvate decarboxylase in a child with an intermittent movement disorder

“…The combination of characteristics is distinct from those described in lactic acidosis (44)(45)(46)(47)(48)(49)(50), thiamine deficiency (51-55), pyruvate carboxylase deficiency (5,56), the subacute sclerosing leukoencephalopathy of Leigh (5,(57)(58)(59)(60)(61), or in the Friedreich-like syndrome described by Dunn, Perry, and Dolman (10,62). Lonsdale and associates (9-11) have recently studied a mentally slow child with hyperpyruvicemia and persistent hyperalanuria and hyperpyruvicemia; the enzymatic defect in this patient has not been described.…”

An inherited defect affecting the tricarboxylic acid cycle in a patient with congenital lactic acidosis

“…6.4.1.1.). Several workers have postulated defects in oxidative metabolism in other such patients, on the basis of accumulation of a-ketoglutaric acid (2,5,6,10), accumulation of glyoxylic acid (5), increased production of lactic acid by exercising muscle (3) and by red blood cells (4), or response to therapy with lipoic acid (5,10 (42). The existence of mutations which cause defects of each of these three types would not be surprising.…”

“…A number of workers have described children with persistent lactic acidosis and diffuse neurologic disease including mental retardation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Defects in gluconeogenetic enzymes have been demonstrated in several of these patients (7,9,11,14).…”

Neurochemical Changes in Leigh's Disease

“…Several authors, impressed with the frequency of lactic acidosis in LD, have studied the ac tivity of enzymes which convert pyruvate into Kreb's cycle intermediates (4)(5)(6). Others, more impressed with the pathological similarities of Leigh's and Wernicke's diseases, have studied the cerebral metabolism of thiamine by LD brains (7).…”