Brain Metabolism

Question 1

Mitochondrial dysfunction

Answer 1

Leigh disease - loss of function of an ETC complex, usually complex 4. Causes rapid loss of neuronal tissue due to reduced ATP production. No cure, presents with seizures, retardation, lactic acidosis.
MELAS - mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. Cause by mutation in leucine tRNA which impairs thiomodification and pauses translation.
MERRF - myoclonic epilepsy with ragged red fibres. Mutation in lysine tRNA, similar to MELAS but with less stroke-like episodes.
KSS - Kearns Sayre Syndrome. Bulk deletion of mtDNA, onset at teenage.
No specific treatments for these but AA and Coenzyme supplementation May help.

Question 2

Lysosomal Dysfunction

Answer 2

Generally the accumulation of non-metabolised macromolecules promotes defects in metabolism, signalling pathways, causes oxidative stress etc. Very poor prognosis for these types of disease, often embryonically lethal.
Metachromic leukodystrophy - arylsulphatase A deficiency resulting in build up in toxic lipids and death usually occurs within 5 years of onset.

Question 3

Peroxisomal dysfunction

Answer 3

Breakdown substrates such as Uric acid, amino acids, fatty acids to provide energy source. Aid in controlling levels of ROS. Diseases here cause profound muscular hypotonia, macrocephaly, visual impairment etc.
Zellweger syndrome - reduced myelination and progressive white matter loss, lethal within first year of life.