Leigh's encephalomyelopathy: an inborn error of gluconeogenesis.

Hyperalaninemia with Pyruvicemia in a Patient Suggestive of Leigh's Encephalomyelopathy

“…COMMENT Hommes et al (1968) reported a defect in pyruvate carboxylase in the liver from a patient with progressive mental and motor retardation whose siblings died with similar symptoms and were diagnosed as subacute necrotizing encephalomye lopathy.…”

“…High levels of blood pyruvate and lactate (Worsley et al 1965, Clayton et al 1967Hommes et al 1968) and low plasma bicarbonate level (Feigin and Wolf 1954;Worsley et al 1965) have been often found in this particular disorder. Furthermore, Dunn and Dolman (1969) pointed out the existence of hyperalaninemia in a case of SNE.…”

Pyruvate Carboxylase Deficiency and Lactic Acidosis in a Retarded Child without Leigh's Disease

“…Likewise, the function of the enzyme in brain is not well understood, although it may be to furnish oxalacetate, and cytosolic acetyl groups and reducing equivalents for various cellular func- Several patients (10,12,19,20,22,40,41) with progressive neurologic deterioration clinically resembling subacute necrotizing encephalomyelopathy (Leigh's disease) (27) have been reported to have hepatic pyruvate carboxylase deficiency. This has led some investigators to conclude that Leigh's disease may be caused by pyruvate carboxylase deficiency.…”

“…The following enzymes involved in glucose or pyruvate metabolism (Fig. I) have been implicated: glucose-6-phosphatase (24,29), fructose-1,6-bisphosphatase (31,32), pyruvate carboxylase (7,10,12,13,19,20,22,37,40,41), and pyruvate dehydrogenase complex (6,15,36,39). Of these enzymes all but the last are required for gluconeogenesis.…”

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

“…Subacute necrotizing encephalomyelopathy or Leigh's disease [10] is an inborn error of metabolism [9] characterized by symmetrical lesions of the brainstem. Two theories on the cause of the disease have been proposed: the first based on the demonstration of a deficiency of pyruvate carboxylase [9] subsequently confirmed by Yoshida et al [18], Delvin et al [6], and Tang et al [17] and the second based on a deficiency of thiamine triphosphate, caused by inhibition of thiamine diphosphate: ATP-phosphotransferase by specific inhibitors circulating in the body fluids of affected patients [3].…”