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Complex I Deficiency

The mitochondrion has two membranes. Embedded in the inner membrane are five protein complexes (complexes I through V), which carry electrons and produce energy in the form of ATP. This chain is known as the respiratory chain (RC).

Defects of complex I, the largest enzyme complex in the RC, are among the most common causes of mitochondrial diseases. Often presenting at birth or in early childhood, complex I deficiency usually causes progressive neuro-degenerative disorders, which are responsible for a variety of clinical symptoms, particularly in organs and tissues that require high energy levels, such as brain, heart, liver, and skeletal muscle. A number of specific mitochondrial disorders have been associated with Complex I deficiency including: Leber hereditary optic neuropathy (LHON), MELAS, and Leigh syndrome (LS).

There are three major forms of Complex I deficiency:

1. Fatal infantile multisystem disorder characterized by encephalopathy, poor muscle tone, developmental delay, heart disease, lactic acidosis, and respiratory failure.

2. Myopathy (muscle disease) starting in childhood or adulthood and characterized by weakness or exercise intolerance.

3. Mitochondrial encephalomyopathy (brain and muscle disease) beginning in childhood or adulthood and involving variable symptom combinations which may include: eye muscle paralysis, pigmentary retinopathy (retinal color changes with loss of vision), hearing loss, neuropathy, seizures, dementia, ataxia, and involuntary movements. This form of Complex I deficiency may cause Leigh syndrome and MELAS.

Most cases of Complex I deficiency result from autosomal recessive inheritance (one mutation from the mother and one from the father). Not infrequently, however, the disorder is maternally inherited. Sporadic and X-linked forms are very rare.

Treatment: As with all mitochondrial diseases, there is no cure for complex I deficiency. A variety of treatments, which may or may not be effective, include: riboflavin, thiamine, biotin, CoQ10, and carnitine. The clinical course and prognosis for Complex I patients is highly variable and may depend on the specific genetic defect, age of onset, organs involved, and other factors."