Investigation of enzyme defects in children with lactic acidosis

Abstract

Screening for enzyme deficiencies was carried out in cultured skin fibroblasts and leukocytes of 19 patients with lactic acidosis and neurological problems. Pyruvate carboxylase deficiency was demonstrated in three cases. Reduced pyruvate oxidation was found in seven cultures; six showed no significant stimulation of the oxidation rate by methylene blue and in three a decreased pyruvate dehydrogenase complex activity was confirmed. Methylene blue restored a near normal oxidation rate in the seventh culture which had decreased cytochrome c oxidase activity.

2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induced alterations of pyruvate carboxylase levels and lactate dehydrogenase isozyme shifts in C57BL/6J male mice

“…Nevertheless, there appears to be sufficient pyruvate reduction to lactate to yield the results shown in Figure 4. Lactate acidosis is characteristic of PC deficiency in humans (29). Presumably, deficiency in PC would lead to an accumulation of pyruvate that may have the following substrate-mediated consequences: (1) An excess of pyruvate accumulation would lead to the reconversion of pyruvate to alanine via a transamination reaction ultimately leading to accumulation of this amino acid.…”

Lactic Acidosis in Paediatrics: Clinical and Laboratory Evaluation

“…Even in laboratories with experience in performing these difficult assays, the success rate in identifying enzymatic causes of lactic acidosis is less than 500/0. 3 , 4 The further elucidation of the nature of these defects at the molecular DNA level will probably make identification, prenatal diagnosis and population screening a much less difficult task.…”

Redox Status in Very-Low Birth-Weight Newborns

“…During the neonatal period, if we exclude congenital heart diseases, shock, recent asphyxia or other kinds of hypoxia, and erroneous blood samplings, hyperlactacidemia is often the first sign of an inborn error of metabolism [1,3]. This group of diseases comprises defects in liver glycogen metabolism, gluconeogenesis, pyruvate oxidative metabolism, Krebs cycle or mitochondrial respiratory chain [4]. While the defect of glycogen metabolism and gluconeogenesis does not involve the oxidation and reduction of NADH/NAD + , in the majority of disorders of pyruvate oxidative metabolism, Krebs cycle or mitochondrial respiratory chain, an abnormal redox status is observed [1,5].…”