Pyruvate dehydrogenase and
pyruvate carboxylase deficiency are the most common disorders in
pyruvate metabolism. Diagnosis is made by enzymatic and
DNA analysis after basic biochemical tests in plasma, urine, and CSF.
Pyruvate dehydrogenase has three main subunits, an additional E3-binding
protein and two complex regulatory
enzymes. Most frequent are deficiencies in PDH-E1α. There is a spectrum of clinical presentations in E1α deficiency, ranging in boys from severe neonatal
lactic acidosis, Leigh
encephalopathy, to later onset of neurological disease such as intermittent
ataxia or
dystonia. Females tend to have a more uniform presentation resembling nonprogressive
cerebral palsy. Neuroradiological abnormalities such as
corpus callosum agenesis are seen more frequently in girls, basal ganglia and midbrain disturbances in boys. Deficiencies in the other subunits have also been described, but in a smaller number of patients.
Pyruvate carboxylase deficiency has three clinical phenotypes. The infantile type is characterized mainly by severe developmental delay,
failure to thrive, and
seizures. The second type is characterized by neonatal onset of severe
lactic acidosis with rigidity and
hypokinesia. A third form is rarer with intermittent episodes of
lactic acidosis and
ketoacidosis. Neuroradiological findings such as
cystic periventricular leukomalacia have been described.