Respiratory chain deficiencies.

[pyruvate dehydrogenase deficiency]

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 .

Diseases
Validation

Diseases presenting "epilepsy" symptom

22q11.2 deletion syndrome

adrenomyeloneuropathy

alexander disease

canavan disease

classical phenylketonuria

cohen syndrome

cowden syndrome

familial hypocalciuric hypercalcemia

gm1 gangliosidosis

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

homocystinuria without methylmalonic aciduria

kabuki syndrome

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neonatal adrenoleukodystrophy

pendred syndrome

phenylketonuria

proteus syndrome

pyruvate dehydrogenase deficiency

sneddon syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated