- An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist

Lactate and pyruvate are normal metabolites. Their plasma levels depend upon the equilibrium between their cytoplasmic production from glycolysis and their consumption by different tissues. Abnormal accumulation of lactic acid is a common cause of pathological metabolic acidosis. In a majority of cases, it is caused by tissue hypoxia resulting from inadequate oxygen supply or poor circulation. Blood lactate accumulates in circulatory collapse, hypoxic insult and other conditions involving failure of cellular respiration. These conditions should be ruled out before investigating for an inborn error of lactate pyruvate. Ketosis is absent in most hyperlactacidemias secondary to tissue hypoxia, while it is a nearly constant finding in most inherited metabolic disorders except pyruvate dehydrogenase deficiency, glycogen storage disorder type I and fatty acid oxidation defects. Following are the inherited metabolic causes of lactic acidosis:

  1. Defects of pyruvate metabolism

    Pyruvate dehydrogenase deficiency
    Pyruvate carboxylase deficiency
  2. Defects of NADH oxidation

    Mitochondrial electron transfer chain defects
  3. Disorders of gluconeogenesis/glycogen storage disorders

    Glucose 6-phosphatase deficiency (GSD I)
    Fructose 1,6- bisphosphatase deficiency
    Phosphoenolpyruvate carboxykinase deficiency
    Glycogen debrancher deficiency (GSD III)
    Glycogen synthase deficiency (GSD 0)
  4. Fatty acid oxidation defects
  5. Defects of biotin metabolism

    Biotinidase deficiency
    Holocarboxylase synthase deficiency
  6. Defects of organic acid metabolism

    Propionic acidemia
    Methylmalonic acidemia
  7. Others

    Hereditary fructose intolerance

The differential diagnosis of elevated lactate in neurometabolic disorders is shown in [Table 6].[31]

rating: 3.15 from 27 votes | updated on: 17 Sep 2008 | views: 206261 |

Rate article:

excellent! bad…