Mitochondrial functions are intimately associated with neurological symptoms. Various clinical and
biological features are suggestive of energy depletion diseases, such as
Leigh syndrome,
Alpers syndrome,
epilepsy (including
myoclonic seizures and
status epilepticus),
stroke-like episodes, and acute
cerebellar ataxia with high
lactate peaks on magnetic resonance spectroscopy. Magnetic resonance imaging (MRI) discloses abnormalities in over 90% of the cases presenting with neurological symptoms. Basal ganglionic involvement, the most frequent imaging sign, can be isolated or combined with subtentorial
atrophy of both the cerebellum and brainstem. MRS monovoxel
proton spectroscopy is useful to reveal high
lactate spikes if placed in the putamen and the cerebellar dentate nucleus.
Lactate and
pyruvate levels are required to exclude
pyruvate dehydrogenase deficiency. However,
lactate may be normal in the CSF. Clinical and biochemical investigations guide molecular studies, with two major heredities:
mtDNA point mutations and autosomal recessive defects that program the majority of respiratory chain subunits. Muscle biopsy is the first test demonstrating the histochemical and ultrastructural alterations in mitochondria, even in diseases in which
myopathy is not clinically prominent, and is also a good tissue for biochemical analysis, as the biopsy is not dangerous for the patient. Negative results in skeletal muscle do not exclude respiratory chain deficiency, and a liver biopsy may be necessary whatever the blood AST and ALT levels, to perform biochemical and molecular investigations. Only the identification of nuclear or mitochondrial mutation confirms the diagnosis.