This is the most common type of respiratory chain
disease. Complex I is the largest respiratory chain complex and involved in
numerous clinical conditions (see Table C-2). Forty-six polypeptide
subunits form Complex I, of which 7 are encoded by mitochondrial DNA (mtDNA) and
the residual 39 by nuclear DNA (nDNA). The major subunits are flavoprotein,
iron-sulphur protein, and hydrophobic fraction. Complex I is involved in the
electron transport from NADH to ubiquinone, from where the electrons are
transported to the next respiratory chain complex. This is the most commonly
identified respiratory chain disease phenotype, which is most likely related to
the large number of subunits encoded by both, nuclear and mitochondrial DNA and the
size of the complex subunit. Complex I deficiency is often part of a combined
deficiency because deficiencies in other complexes may result in a loss of Complex
I function. It is the result of a number of situations where mtDNA point mutations
are associated with deletions. In the absence of known mtDNA abnormalities, it may
be associated with fatal infantile encephalomyopathy. As an isolated deficit, the
clinical presentation occurs at the age of 4 to 5 months and in about 70% of
patients death occurs within 2 years. Severe lactic acidosis occurs in 85% of
patients. Most infants also present with severe cardiomyopathy, childhood
encephalopathy, macrocephaly with progressive leukodystrophy, hepatomegaly and real
tubulopathy. The most frequent myopathy is known as MELAS syndrome.
NADH-Coenzyme Q Reductase Deficiency; NADH-Ubiquinone Oxidoϲeductase Deficiency.
The estimated incidence for all forms of respiratory chain diseases combined is approximately 1 in 10,000
live births. The male-to-female ratio is approximately 3.5:1.
Inheritance is usually autosomal recessive. It can also be caused, as with all mitochondrial
encephalopathies, by mutations in multiple different genes. Complex I deficiency presents both nuclear-encoded and
mitochondrial-encoded mutations. Human complex I (NADH-ubiquinone reductase) consists of at least 36 nuclear-encoded
and 7 mitochondrial-encoded subunits. Mutations in any of these subunits can cause the disorder, which explains the
complexity of this disorder.
Cheam EW, Critchley LA: Anesthesia for a child with complex I respiratory
chain enzyme deficiency J Clin Anesth